Peripheral Neutrophil-to-Lymphocyte Ratio in stable state Bronchiectasis as a Marker of Disease Severity: A Retrospective Cohort Study in North Taiwan

Peripheral Neutrophil-to-Lymphocyte Ratio in stable state Bronchiectasis as a Marker of Disease Severity: A Retrospective Cohort Study in North Taiwan | 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 Peripheral Neutrophil-to-Lymphocyte Ratio in stable state Bronchiectasis as a Marker of Disease Severity: A Retrospective Cohort Study in North Taiwan Meng-Heng Hsieh, Chiung-Hsin Chang, Chun-Yu Lin, Yueh-Fu Fang, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9071727/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background We aimed to evaluate the clinical relevance of the neutrophil-to-lymphocyte ratio (NLR) and the severity scoring systems in the potential diagnostic and prognostic value in stable non-CF bronchiectasis. Methods This retrospective study was conducted from 146 patients with stable non-CF bronchiectasis between January 2017 and August 2025. Participants were stratified into two groups based on the optimal AUC-derived NLR cut-off value of 2.76. Results Patients with NLR ≥ 2.76 had significantly higher proportions of current and former smokers ( p = 0.031) and higher smoking amounts (packs/year) ( p = 0.031). The FEV1% was significantly higher in the NLR < 2.76 group ( p = 0.021). The AUC between BSI, FACED and NLR were 0.716 vs. 0.706 ( p = 0.025) and 0.706 vs. 0.636 ( p = 0.032), respectively. Severe BSI scores were significantly different for survival rate (HR = 0.386, p = 0.008). The moderate cases of FACED score showed a significant difference (HR = 0.238, p = 0.004) when compared with mild scores. NLR ≥ 2.76 patients demonstrated a higher death rate than NLR < 2.76 (HR = 0.514, p = 0.078). Conclusions NLR is associated with non-cystic fibrosis bronchiectasis severity and mortality and may help predict survival rate that may serve as potential predictors of clinical outcomes in stable non-CF bronchiectasis. Bronchiectasis Neutrophil-to-lymphocyte ratio Neutrophil FACED Score BSI Score Figures Figure 1 Figure 2 Figure 3 Introduction Non-cystic fibrosis (CF) bronchiectasis is a chronic respiratory disorder characterized by irreversible bronchial dilation, persistent airway inflammation, and recurrent infections that progressively damage the airways, leading to pulmonary dysfunction 1 – 3 . The global prevalence of non-CF bronchiectasis has been increasing 4 – 5 , likely due to improved diagnostic capabilities, particularly with the use of high-resolution computed tomography (HRCT). Airway inflammation in bronchiectasis is closely associated with neutrophil-driven processes, with neutrophils serving as key mediators of mucociliary dysfunction and structural lung damage 2 , 6 , as well as being strong predictors of exacerbation frequency and disease progression 7 . Recently, the neutrophil-to-lymphocyte ratio (NLR) has gained increasing interest as a potential marker of disease activity and prognosis, as it is an easily obtainable biomarker of systemic inflammation, derived by dividing the absolute neutrophil count by the absolute lymphocyte count. The pathogenic role of neutrophil-derived proteolytic enzymes, particularly neutrophil elastase and matrix metalloproteinases enzymes 8 – 9 . Chronic bronchial infection is strongly associated with heightened airway inflammation and represents a major determinant in widely used severity scoring systems, including the Bronchiectasis Severity Index (BSI) and FACED score, supporting the clinical utility of these parameters in assessing disease severity. Given the few reported associations between NLR and established severity scoring systems, by examining NLR in parallel with validated severity scoring systems, this study aimed to advance current understanding of their clinical relevance in assessing disease burden and forecasting outcomes in patients with stable non-CF bronchiectasis. Materials and methods Study population and design This retrospective study included data from 146 patients with stable-state non-cystic fibrosis bronchiectasis who were followed at the outpatient clinic of Linkou Chang Gung Memorial Hospital, Taiwan, between January 2017 and August 2025. The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital (Approval No. 202101879B0). The need for informed consent was waived owing to the retrospective nature of the study and the lack of any intervention affecting patient care. All collected data were anonymized, stored in an encrypted database, and managed in compliance with patient privacy regulations. All included patients met the following criteria: bronchiectasis confirmed by HRCT of the chest and an idiopathic etiology, with no clinical features suggestive of cystic fibrosis. Patients with bronchiectasis of a defined etiology such as primary ciliary dyskinesia, allergic bronchopulmonary aspergillosis, or common variable immunodeficiency were excluded. Further exclusion criteria included antibiotic use within the preceding three weeks, as well as hepatic failure, malignancy, or pregnancy. Additional inclusion criteria required chronic sputum production (≥ 10 mL daily), the absence of other major pulmonary diseases, and a stable clinical condition defined by no change in symptoms during the three weeks prior to enrollment. The demographic and clinical variables were extracted from medical records. Data required to calculate the BSI and FACED scores were collected. Disease severity was categorized according to each scoring system as follows: mild (BSI score ≤ 4, FACED score ≤ 2), moderate (BSI score 5–8, FACED score 3–4), and severe (BSI score ≥ 9, FACED score ≥ 5). To investigate the diagnostic and prognostic relevance of NLR in bronchiectasis, NLR was also evaluated. Patients were stratified into two groups according to the optimal NLR threshold, which was determined based on the area under the receiver operating characteristic (ROC) curve for mortality prediction (Fig. 1 ). Definition of abbreviations: BMI: body mass index; ABPA: Allergic bronchopulmonary aspergillosis; COPD=chronic obstructive pulmonary disease; T2DM: Type 2 Diabetes Mellitus; CAD: Coronary Artery Disease BSI: bronchiectasis severity index; Data are shown as means ± SD (* P , 0.05) or unless otherwise stated. Differences in continuous variables were evaluated using ANOVA followed by Bonferroni’s test. Statistical analysis Statistical analyses were conducted using SPSS version 14.0 (IBM SPSS Inc., Chicago, IL, USA). Independent Student’s t-tests were applied to compare clinical parameters between two groups, while one-way ANOVA was used for comparisons involving more than two groups. Non-parametric data were analyzed using the Chi-square test. Receiver operating characteristic (ROC) curves were generated, and areas under the curve (AUCs) for correlated ROC curves were compared using DeLong’s test where applicable. Optimal cut-off points were determined using Youden’s index (sensitivity + [1 − specificity]). After identifying the NLR cut-off value that yielded the highest AUC, survival curves were generated to compare outcomes between patients above and below this threshold. Survival analysis was performed using the Kaplan–Meier method, and group differences were assessed with the log-rank test. Participants were subsequently stratified into two groups based on the optimal AUC-derived NLR cut-off value of 2.76. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. Results Patient’s characteristics Data from 213 patients diagnosed with non-CF bronchiectasis were collected from the chest outpatient department. Of these, 146 patients who met the inclusion criteria were included in the analysis, as shown in Fig. 1 . Following the initial evaluation of patient characteristics based on baseline NLR, results are shown in Table 1 . The patients were stratified using an NLR cut-off value of 2.76 into two groups. Non-CF bronchiectasis patients with NLR ≥ 2.76 were older (66.19 ± 11.13 years vs. 65.44 ± 10.60 years, p = 0.678) compared to patients with NLR < 2.76. However, BMI was almost similar between the two groups (22.68 ± 4.21 vs. 22.30 ± 4.21, p = 0.585). Patients with NLR ≥ 2.76 has significantly increased in current and former smokers (0.25 ± 0.66 vs. 0.54 ± 0.88, p = 0.031) and higher smoking amounts (packs/year) (0.33 ± 1.04 vs. 0.84 ± 1.57, p = 0.031) compared with patients with NLR < 2.76. The FEV1% was significantly higher in the NLR < 2.76 group (66.93 ± 22.16 vs. 57.63 ± 20.89, p = 0.021). Moreover, FVC% tended to be higher in the NLR < 2.76 group (71.04 ± 22.07 vs. 63.50 ± 20.3, p = 0.056). In addition, COPD was significantly more prevalent in the NLR ≥ 2.76 group (14 [19.72%] vs. 31 [41.33%], p = 0.004). The chronic colonization tended to be higher in the NLR ≥ 2.76 group (70 [98.6%] vs. 75 [100%], p = 0.059). Pseudomonas colonization was also higher in the NLR ≥ 2.76 group but not significantly different (38 [53.52%] vs. 52 [69.33%], p = 0.09). However, P. aeruginosa infection was significantly different between groups (5 [7.04%] vs. 12 [16%], p = 0.026). Furthermore, BSI and FACED did not differ significantly between the two groups (2.9 ± 1.67 vs. 2.45 ± 1.57, p = 0.136; 8.08 ± 3.59 vs. 9.31 ± 4.38, p = 0.099, respectively). Additionally, ICS used tended to be higher in patients with NLR ≥ 2.76 (38 [53.52%] vs. 52 [69.33%], p = 0.051). The total white blood cell (WBC) count was significantly higher in patients with NLR ≥ 2.76 (6780.28 ± 2134.65 vs. 10501.87 ± 9111.08, p = 0.001) Table 2 Area under the curve (AUC) for mortality at different time points between BSI, FACED and NLR BSI FACED NLR Mortality 0.716 (0.567–0.864) 0.706 (0.547–0.865) 0.636 (0.465–0.809) # p = 0.025 @ p = 0.032 * p = 0.155 Data are presented as area under the curve (95% CI). p -values calculated using DeLong’s test for two correlated ROC curves. #Comparison of ROC curves between BSI and FACED; comparison of ROC curves between FACED and NLR; comparison of ROC curves between NLR and BSI. BSI: bronchiectasis severity index; NLR: Neutrophil-to-Lymphocyte ratio. Receiver operating characteristic analysis The AUCs for overall mortality for the BSI, FACED scores, and NLR were 0.716 vs. 0.706 ( p = 0.025) and 0.706 vs. 0.636 ( p = 0.032), respectively. The AUCs for mortality at specified time points for BSI, FACED scores, and NLR are presented in Fig. 2 and Table 2 . Survival analysis Among the 146 study patients, 42 (28.7%) died during the study period. Mortality varied according to BSI and FACED scores, from 20% and 22.22% in mild cases to 43.86% and 54.54% in severe cases. Using the NLR cut-off value of 2.76, mortality was 21.73% in those with NLR < 2.76 and 35.06% in those with NLR ≥ 2.76 ( p = 0.078) (Fig. 3 ). (A) (B) Determinant factors of NLR The results of the univariate Cox proportional hazards analysis are shown in Table 3 . There tended to be a significant difference between mild and moderate BSI scores (hazard ratio = 0.320, p = 0.066). However, severe BSI scores were significantly different for survival rate (hazard ratio = 0.386, p = 0.008) when compared with mild BSI scores. Regarding the FACED score, moderate cases showed a significant survival difference (hazard ratio = 0.238, p = 0.004) when compared with mild FACED scores. The severe group also tended to have a different survival rate compared with the mild group (hazard ratio = 0.386, p = 0.062). Patients with NLR ≥ 2.76 demonstrated a higher death rate than those with NLR < 2.76 (hazard ratio = 0.514, p = 0.078). Table 3 Univariate Cox proportional hazard analysis of BSI, FACED scores, and NLR for mortality during study period BSI Subjects, n Mortality, n (%) Hazard ratio (95% CI) p -value Mild 20 4 (20%) Reference - Moderate 95 22 (23.16%) 0.320 (0.095–1.078) 0.066 Severe 57 25 (43.86%) 0.386 (0.190–0.783) 0.008 FACED Mild 90 20 (22.22%) Reference - Moderate 60 19 (31.67%) 0.238 (0.09–0.631) 0.004 Severe 22 12 (54.54%) 0.386 (0.142–1.05) 0.062 NLR < 2.73 69 15 (21.73%) Reference - ≥2.73 77 27 (35.06%) 0.514 (0.246–1.077) 0.078 BSI: bronchiectasis severity index; NLR: neutrophil per lymphocyte ratio. Discussion In the present study demonstrate that the appropriate cut-off value of NLR was 2.76, and that NLR is associated with both disease severity (mild, moderate, and severe) and mortality in bronchiectasis patients. Several studies have proposed NLR threshold values that may be used to predict clinical severity, risk of exacerbation, and even mortality among patients with bronchiectasis. Kwok et al . reported the appropriate thresholds to predict the need for hospitalization for bronchiectasis exacerbation during a 4-year follow-up 10 . Elevated NLR values have been reported in patients with positive sputum cultures and were also significantly higher in patients with bronchiectasis exacerbation when compared with healthy controls and correlates with clinical severity in bronchiectasis patients also exhibits good prognostic capacity for predicting future exacerbations 11 – 12 . Moreover, Nacaroglu et al . demonstrated that NLR can be used as a biomarker to reflect chronic inflammation and acute exacerbations of bronchiectasis in children 13 . Our findings demonstrated that the BSI and FACED scores did not differ significantly between the groups. These results are consistent with previous reports, which also identified that BSI and FACED scores were not significantly correlated with NLR 14 . However, in the current study, the survival rate in patients with severe BSI scores and moderate FACED scores differed significantly when compared with those with mild scores. Additionally, our previous study demonstrated that the distance–saturation product (DSP) and lowest oxygen saturation during the 6-min walk test exhibited predictive power comparable to that of validated BSI and FACED scores in non-CF bronchiectasis patients 15 . It should be emphasized that both the BSI and FACED scores incorporate forced expiratory volume in one second (FEV₁), which is closely associated with impaired gas exchange and obstructive pulmonary dysfunction. During exacerbations, neutrophils migrate to the airways and release neutrophil elastase and matrix metalloproteinases enzymes, which drive extracellular matrix degradation and epithelial injury, ultimately resulting in airway structural destruction. The consequent disruption promotes bacterial colonization and sustains a cycle of inflammation, tissue injury, and progressive bronchial dysfunction that contributes to the development and progression of bronchiectasis 8 – 9 , 16 . In the present study, COPD prevalence was significantly higher in patients with NLR ≥ 2.76, whereas ICS use tended to be higher ( p = 0.051) compared with patients with NLR < 2.76. Several studies have demonstrated that neutrophils have a strong relationship with COPD as a biomarker that can predict the effects of ICS in clinical practice, which are anti-inflammatory agents commonly prescribed for patients with COPD 17 . Although Sakurai et al . demonstrated that NLR emerged as a predictor of exacerbations, one possible explanation is the relatively high rate of ICS prescription in their cohort compared with previous studies. Although ICS therapy is widely used, it may not adequately prevent exacerbations in COPD patients with elevated NLR 18 . Moreover, in the present study, we observed significantly different of current and past smokers, including greater smoking amounts (packs/year), in patients with NLR ≥ 2.76. This finding is not surprising, as prior evidence indicates that cigarette smoking exerts pro-inflammatory effects on the lungs even after smoking cessation in COPD patients 19 . The persistent inflammatory response in the lungs, characterized by ongoing neutrophil recruitment and activation as previously described, contributes to the development and progression of emphysema and is closely associated with the severity of airflow limitation 20 . Furthermore, we observed significant differences in P. aeruginosa isolation among the NLR groups. This is consistent with previous studies showing that NLR values were significantly different between patients with positive versus negative sputum cultures and were particularly elevated in those infected with P. aeruginosa 11 . Our study has several important limitations. First, as a retrospective study, the sample size was limited, underscoring the need for larger, prospective investigations. Second, all participants were recruited from a single center, which may restrict the generalizability of our findings. Third, the study was conducted during the COVID-19 pandemic, leading to loss of follow-up in some patients. Finally, larger multicenter studies with broader patient populations are required to validate and extend our results. Conclusions This retrospective study demonstrates that NLR is associated with non-cystic fibrosis bronchiectasis severity and mortality and may help predict survival rate. This information suggests that NLR and severity scoring systems may serve as potential predictors of clinical outcomes, being inexpensive and providing useful measures for assessing disease burden and prognosis. Declarations Ethics approval and consent to participate The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital (Approval No. 202101879B0). All collected data were anonymized, stored in an encrypted database, and managed in compliance with patient privacy regulations. The need for informed consent was waived owing to the retrospective nature of the study and the lack of any intervention affecting patient care. Consent for publication Not applicable. This study does not contain any individual person’s data in any form including images or videos. Competing interests The authors declare no competing interests. Data Available Statement Data available on request from the authors. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not for profit sectors. Authors Contributions All the authors contributed to conception and design of the study. Meng-Heng Hsieh, Horng-Chyuan Lin and Jureeporn U-pathi: analyzed and interpreted the data. Meng-Heng Hsieh and Jureeporn U-pathi: drafted the manuscript. Meng-Heng Hsieh, Chiung-Hsin Chang, Chun-Yu Lin, Yueh-Fu Fang, Bing-Chen Wu, Mei-Yuan Teo, Hsin-I Cheng, and Tzu-Hsuan Chiu: provided the study materials, selected patients, collected and assembled data. All the authors draft the article or revising it critically for important intellectual content, have agreed on the journal to which the article has been submitted, approved the final manuscript and agreed to be accountable for all aspects of the work. Acknowledgements The authors would like to thank all the participants in the study also the investigators and members of the Department of Thoracic Medicine for their efforts. References Flume PA, Chalmers JD, Olivier KN. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet. 2018;392(10150):880–90. 10.1016/S0140-6736(18)31767-7 . Polverino E, Goeminne PC, McDonnell MJ, et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017;50(3):1700629. 10.1183/13993003.00629-2017 . Fuschillo S, De Felice A, Balzano G. Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms. Eur Respir J. 2008;31(2):396–406. 10.1183/09031936.00069007 . Quint JK, Millett ER, Joshi M, et al. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study. Eur Respir J. 2016;47(1):186–93. 10.1183/13993003.01033-2015 . Weycker D, Hansen GL, Seifer FD. Prevalence and incidence of noncystic fibrosis bronchiectasis among US adults in 2013. Chron Respir Dis. 2017;14(4):377–84. 10.1177/1479972317709649 . Chang CL, Sheu CC, Wang PH, et al. Clinical significance of respiratory bacteria and mycobacteria isolates in adult bronchiectasis in Taiwan. ERJ Open Res. 2025;11(4):00865–2024. 10.1183/23120541.00865-2024 . Chen YF, Chang CL, Hou HH, et al. The impact of COPD-bronchiectasis association on clinical outcomes: insights from East Asian cohorts validating the ROSE criteria. ERJ Open Res. 2025;11(2):00626–2024. 10.1183/23120541.00626-2024 . King PT. The pathophysiology of bronchiectasis. Int J Chron Obstruct Pulmon Dis. 2009;4:411–9. 10.2147/copd.s6133 . Chalmers JD, Smith MP, McHugh BJ, Doherty C, Govan JR, Hill AT. Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2012;186(7):657–65. 10.1164/rccm.201203-0487OC . Kwok WC, Ho JCM, Lam DCL, Ip MSM, Tam TCC. Baseline neutrophil-to-lymphocyte ratio as a predictor of response to hospitalized bronchiectasis exacerbation risks. Eur Clin Respir J. 2024;11(1):2372901. 10.1080/20018525.2024.2372901 . Georgakopoulou VE, Trakas N, Damaskos C, et al. Neutrophils to Lymphocyte Ratio as a Biomarker in Bronchiectasis Exacerbation: A Retrospective Study. Cureus. 2020;12(8):e9728. 10.7759/cureus.9728 . Martinez-García MÁ, Olveira C, Girón R, et al. Peripheral Neutrophil-to-Lymphocyte Ratio in Bronchiectasis: A Marker of Disease Severity. Biomolecules. 2022;12(10):1399. 10.3390/biom12101399 . Nacaroglu HT, Erdem SB, Karaman S, Yazici S, Can D. Can mean platelet volume and neutrophil-to-lymphocyte ratio be biomarkers of acute exacerbation of bronchiectasis in children? Cent Eur J Immunol. 2017;42(4):358–62. 10.5114/ceji.2017.72808 . Coban H, Gungen AC. Is There a Correlation between New Scoring Systems and Systemic Inflammation in Stable Bronchiectasis? Can Respir J. 2017; 2017:9874068. 10.1155/2017/9874068 Lin CY, Hsieh MH, Fang YF, et al. Predicting mortality in non-cystic fibrosis bronchiectasis patients using distance-saturation product. Ann Med. 2021;53(1):2034–40. 10.1080/07853890.2021.1999490 . Giam YH, Shoemark A, Chalmers JD. Neutrophil dysfunction in bronchiectasis: an emerging role for immunometabolism. Eur Respir J. 2021;58(2):2003157. 10.1183/13993003.03157-2020 . Singh D, Agusti A, Anzueto A, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J. 2019;53(5):1900164. 10.1183/13993003.00164-2019 . Sakurai K, Chubachi S, Irie H, et al. Clinical utility of blood neutrophil-lymphocyte ratio in Japanese COPD patients. BMC Pulm Med. 2018;18(1):65. 10.1186/s12890-018-0639-z . Rutgers SR, Postma DS, ten Hacken NH, et al. Ongoing airway inflammation in patients with COPD who do not currently smoke. Thorax. 2000;55(1):12–8. 10.1136/thorax.55.1.12 . Kido T, Tamagawa E, Bai N, et al. Particulate matter induces translocation of IL-6 from the lung to the systemic circulation. Am J Respir Cell Mol Biol. 2011;44(2):197–204. 10.1165/rcmb.2009-0427OC . Table 1 Table 1 is available in the Supplementary Files section. 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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-9071727","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":606613752,"identity":"ddd7427f-7f3d-46e7-b153-55fa5795c4b1","order_by":0,"name":"Meng-Heng Hsieh","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Meng-Heng","middleName":"","lastName":"Hsieh","suffix":""},{"id":606613753,"identity":"66914523-8c2f-42d4-bc22-8639d602feab","order_by":1,"name":"Chiung-Hsin Chang","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chiung-Hsin","middleName":"","lastName":"Chang","suffix":""},{"id":606613755,"identity":"b9b708dc-0340-4fa7-8f79-8550f941e486","order_by":2,"name":"Chun-Yu Lin","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chun-Yu","middleName":"","lastName":"Lin","suffix":""},{"id":606613756,"identity":"0ec3ba8c-5f78-4590-8046-9c171a35434d","order_by":3,"name":"Yueh-Fu Fang","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yueh-Fu","middleName":"","lastName":"Fang","suffix":""},{"id":606613757,"identity":"a315af2f-9214-4e9c-9918-063de22e9994","order_by":4,"name":"Bing-Chen Wu","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bing-Chen","middleName":"","lastName":"Wu","suffix":""},{"id":606613758,"identity":"d87361fe-6219-4f1b-a168-ece93810e2a7","order_by":5,"name":"Mei-Yuan Teo","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mei-Yuan","middleName":"","lastName":"Teo","suffix":""},{"id":606613759,"identity":"68d17ac5-b5a4-454b-bd0f-2ac9e4c41800","order_by":6,"name":"Hsin-I Cheng","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hsin-I","middleName":"","lastName":"Cheng","suffix":""},{"id":606613760,"identity":"a2bbdf9c-3c8a-47b1-bc21-ae586ea39af3","order_by":7,"name":"Tzu-Hsuan Chiu","email":"","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tzu-Hsuan","middleName":"","lastName":"Chiu","suffix":""},{"id":606613762,"identity":"0925318d-1ff4-4f9a-8598-38dac3ae678c","order_by":8,"name":"Jureeporn U-pathi","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Jureeporn","middleName":"","lastName":"U-pathi","suffix":""},{"id":606613768,"identity":"9ef685bb-0321-4d92-a9c0-3c1aa2b1e78d","order_by":9,"name":"Horng-Chyuan Lin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIie3PMUsDMRTA8ScPesu7Zn2lxc/wJFARCn6VwoG3dLixg2Anp4JroR+jXyAl0C43S0HBKwfO112qr+ok3p2jQ/6EQEh+JAEIhf5hXYToUNEIjS7WFThqJR3UwYObqDeDM8+fBE8bUk9Og0beiAPU8w7aSRRvCp5g3z5uC8fwPLiMHhxm07eGh3VTyfKOHT5NxGXwSldzD7jIG25BEu7NKVECeosn2SWA8X0LiY98t1qmhf5FyUup5NhIhkwkKP2xfJEdKpk1EmuZxsj6F8+iJE903thaYkx+sa/oHc0yLQ/V1F/Ldr0v6fa8lvzo+znur+dDoVAo9HsfXPJKaL5/GTcAAAAASUVORK5CYII=","orcid":"","institution":"Chang Gung Memorial Hospital","correspondingAuthor":true,"prefix":"","firstName":"Horng-Chyuan","middleName":"","lastName":"Lin","suffix":""}],"badges":[],"createdAt":"2026-03-09 10:39:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9071727/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9071727/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104867611,"identity":"74954419-c569-4c37-a745-45393fdb9bdd","added_by":"auto","created_at":"2026-03-18 07:13:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":135163,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of this cohort study. A total of 213 patients with non-cystic fibrosis bronchiectasis.\u003c/p\u003e","description":"","filename":"Screenshot20260317051532.png","url":"https://assets-eu.researchsquare.com/files/rs-9071727/v1/aed5f74f2d655d2830bf77c8.png"},{"id":104867655,"identity":"585d7a07-610f-460c-a082-e908c0929a3b","added_by":"auto","created_at":"2026-03-18 07:13:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":80461,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves of survival in the patients with non-cystic fibrosis bronchiectasis. ROC: receiver operating characteristic; BSI: bronchiectasis severity index; NLR: neutrophil per lymphocyte ratio.\u003c/p\u003e","description":"","filename":"Screenshot20260317051600.png","url":"https://assets-eu.researchsquare.com/files/rs-9071727/v1/e4fc3ef2328e921a777dea06.png"},{"id":104867610,"identity":"05bda55d-a387-4b96-ade9-31dedaff466a","added_by":"auto","created_at":"2026-03-18 07:13:26","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":491717,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival of the patients with non-cystic fibrosis bronchiectasis. (A) Survival in relation to BSI score, (B) Survival in relation to FACED score, (C) Survival in relation to NLR score\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9071727/v1/9af099816f80a06937490f49.png"},{"id":106207897,"identity":"f220aebc-d65b-4dd3-9167-c7e2129ecd04","added_by":"auto","created_at":"2026-04-06 06:11:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1312098,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9071727/v1/73955353-4bd1-4921-bf4a-975ee4079dac.pdf"},{"id":104867606,"identity":"d7357d19-6e16-48cb-acac-a2cb10b95bf2","added_by":"auto","created_at":"2026-03-18 07:13:25","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17518,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9071727/v1/1bae3136009a1b1169c118a9.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Peripheral Neutrophil-to-Lymphocyte Ratio in stable state Bronchiectasis as a Marker of Disease Severity: A Retrospective Cohort Study in North Taiwan","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNon-cystic fibrosis (CF) bronchiectasis is a chronic respiratory disorder characterized by irreversible bronchial dilation, persistent airway inflammation, and recurrent infections that progressively damage the airways, leading to pulmonary dysfunction\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The global prevalence of non-CF bronchiectasis has been increasing\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e, likely due to improved diagnostic capabilities, particularly with the use of high-resolution computed tomography (HRCT).\u003c/p\u003e \u003cp\u003eAirway inflammation in bronchiectasis is closely associated with neutrophil-driven processes, with neutrophils serving as key mediators of mucociliary dysfunction and structural lung damage\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e, as well as being strong predictors of exacerbation frequency and disease progression\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Recently, the neutrophil-to-lymphocyte ratio (NLR) has gained increasing interest as a potential marker of disease activity and prognosis, as it is an easily obtainable biomarker of systemic inflammation, derived by dividing the absolute neutrophil count by the absolute lymphocyte count. The pathogenic role of neutrophil-derived proteolytic enzymes, particularly neutrophil elastase and matrix metalloproteinases enzymes\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Chronic bronchial infection is strongly associated with heightened airway inflammation and represents a major determinant in widely used severity scoring systems, including the Bronchiectasis Severity Index (BSI) and FACED score, supporting the clinical utility of these parameters in assessing disease severity.\u003c/p\u003e \u003cp\u003eGiven the few reported associations between NLR and established severity scoring systems, by examining NLR in parallel with validated severity scoring systems, this study aimed to advance current understanding of their clinical relevance in assessing disease burden and forecasting outcomes in patients with stable non-CF bronchiectasis.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy population and design\u003c/h2\u003e\n \u003cp\u003eThis retrospective study included data from 146 patients with stable-state non-cystic fibrosis bronchiectasis who were followed at the outpatient clinic of Linkou Chang Gung Memorial Hospital, Taiwan, between January 2017 and August 2025. The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital (Approval No. 202101879B0). The need for informed consent was waived owing to the retrospective nature of the study and the lack of any intervention affecting patient care. All collected data were anonymized, stored in an encrypted database, and managed in compliance with patient privacy regulations.\u003c/p\u003e\n \u003cp\u003eAll included patients met the following criteria: bronchiectasis confirmed by HRCT of the chest and an idiopathic etiology, with no clinical features suggestive of cystic fibrosis. Patients with bronchiectasis of a defined etiology such as primary ciliary dyskinesia, allergic bronchopulmonary aspergillosis, or common variable immunodeficiency were excluded. Further exclusion criteria included antibiotic use within the preceding three weeks, as well as hepatic failure, malignancy, or pregnancy. Additional inclusion criteria required chronic sputum production (\u0026ge;\u0026thinsp;10 mL daily), the absence of other major pulmonary diseases, and a stable clinical condition defined by no change in symptoms during the three weeks prior to enrollment. The demographic and clinical variables were extracted from medical records. Data required to calculate the BSI and FACED scores were collected. Disease severity was categorized according to each scoring system as follows: mild (BSI score\u0026thinsp;\u0026le;\u0026thinsp;4, FACED score\u0026thinsp;\u0026le;\u0026thinsp;2), moderate (BSI score 5\u0026ndash;8, FACED score 3\u0026ndash;4), and severe (BSI score\u0026thinsp;\u0026ge;\u0026thinsp;9, FACED score\u0026thinsp;\u0026ge;\u0026thinsp;5). To investigate the diagnostic and prognostic relevance of NLR in bronchiectasis, NLR was also evaluated. Patients were stratified into two groups according to the optimal NLR threshold, which was determined based on the area under the receiver operating characteristic (ROC) curve for mortality prediction (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eDefinition of abbreviations: BMI: body mass index; ABPA: Allergic bronchopulmonary aspergillosis; COPD=chronic obstructive pulmonary disease; T2DM: Type 2 Diabetes Mellitus; CAD: Coronary Artery Disease BSI: bronchiectasis severity index; Data are shown as means\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (*\u003cem\u003eP\u003c/em\u003e, 0.05) or unless otherwise stated. Differences in continuous variables were evaluated using ANOVA followed by Bonferroni\u0026rsquo;s test.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical analysis\u003c/h2\u003e\n \u003cp\u003eStatistical analyses were conducted using SPSS version 14.0 (IBM SPSS Inc., Chicago, IL, USA). Independent Student\u0026rsquo;s t-tests were applied to compare clinical parameters between two groups, while one-way ANOVA was used for comparisons involving more than two groups. Non-parametric data were analyzed using the Chi-square test. Receiver operating characteristic (ROC) curves were generated, and areas under the curve (AUCs) for correlated ROC curves were compared using DeLong\u0026rsquo;s test where applicable. Optimal cut-off points were determined using Youden\u0026rsquo;s index (sensitivity + [1\u0026thinsp;\u0026minus;\u0026thinsp;specificity]). After identifying the NLR cut-off value that yielded the highest AUC, survival curves were generated to compare outcomes between patients above and below this threshold. Survival analysis was performed using the Kaplan\u0026ndash;Meier method, and group differences were assessed with the log-rank test. Participants were subsequently stratified into two groups based on the optimal AUC-derived NLR cut-off value of 2.76. All statistical tests were two-sided, and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\n \n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePatient\u0026rsquo;s characteristics\u003c/h2\u003e \u003cp\u003eData from 213 patients diagnosed with non-CF bronchiectasis were collected from the chest outpatient department. Of these, 146 patients who met the inclusion criteria were included in the analysis, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Following the initial evaluation of patient characteristics based on baseline NLR, results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The patients were stratified using an NLR cut-off value of 2.76 into two groups. Non-CF bronchiectasis patients with NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 were older (66.19\u0026thinsp;\u0026plusmn;\u0026thinsp;11.13 years vs. 65.44\u0026thinsp;\u0026plusmn;\u0026thinsp;10.60 years, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.678) compared to patients with NLR\u0026thinsp;\u0026lt;\u0026thinsp;2.76. However, BMI was almost similar between the two groups (22.68\u0026thinsp;\u0026plusmn;\u0026thinsp;4.21 vs. 22.30\u0026thinsp;\u0026plusmn;\u0026thinsp;4.21, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.585). Patients with NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 has significantly increased in current and former smokers (0.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66 vs. 0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031) and higher smoking amounts (packs/year) (0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04 vs. 0.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031) compared with patients with NLR\u0026thinsp;\u0026lt;\u0026thinsp;2.76. The FEV1% was significantly higher in the NLR\u0026thinsp;\u0026lt;\u0026thinsp;2.76 group (66.93\u0026thinsp;\u0026plusmn;\u0026thinsp;22.16 vs. 57.63\u0026thinsp;\u0026plusmn;\u0026thinsp;20.89, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021). Moreover, FVC% tended to be higher in the NLR\u0026thinsp;\u0026lt;\u0026thinsp;2.76 group (71.04\u0026thinsp;\u0026plusmn;\u0026thinsp;22.07 vs. 63.50\u0026thinsp;\u0026plusmn;\u0026thinsp;20.3, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.056). In addition, COPD was significantly more prevalent in the NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 group (14 [19.72%] vs. 31 [41.33%], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). The chronic colonization tended to be higher in the NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 group (70 [98.6%] vs. 75 [100%], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.059). Pseudomonas colonization was also higher in the NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 group but not significantly different (38 [53.52%] vs. 52 [69.33%], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.09). However, \u003cem\u003eP. aeruginosa\u003c/em\u003e infection was significantly different between groups (5 [7.04%] vs. 12 [16%], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026). Furthermore, BSI and FACED did not differ significantly between the two groups (2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67 vs. 2.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.136; 8.08\u0026thinsp;\u0026plusmn;\u0026thinsp;3.59 vs. 9.31\u0026thinsp;\u0026plusmn;\u0026thinsp;4.38, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.099, respectively). Additionally, ICS used tended to be higher in patients with NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 (38 [53.52%] vs. 52 [69.33%], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.051). The total white blood cell (WBC) count was significantly higher in patients with NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 (6780.28\u0026thinsp;\u0026plusmn;\u0026thinsp;2134.65 vs. 10501.87\u0026thinsp;\u0026plusmn;\u0026thinsp;9111.08, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eArea under the curve (AUC) for mortality at different time points between BSI, FACED and NLR\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFACED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNLR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eMortality\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.716 (0.567\u0026ndash;0.864)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.706 (0.547\u0026ndash;0.865)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.636 (0.465\u0026ndash;0.809)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003csup\u003e#\u003c/sup\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003csup\u003e@\u003c/sup\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003csup\u003e\u003cem\u003e*\u003c/em\u003e\u003c/sup\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData are presented as area under the curve (95% CI). \u003cem\u003ep\u003c/em\u003e-values calculated using DeLong\u0026rsquo;s test for two correlated ROC curves. #Comparison of ROC curves between BSI and FACED; comparison of ROC curves between FACED and NLR; comparison of ROC curves between NLR and BSI. BSI: bronchiectasis severity index; NLR: Neutrophil-to-Lymphocyte ratio.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eReceiver operating characteristic analysis\u003c/h3\u003e\n\u003cp\u003eThe AUCs for overall mortality for the BSI, FACED scores, and NLR were 0.716 vs. 0.706 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025) and 0.706 vs. 0.636 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032), respectively. The AUCs for mortality at specified time points for BSI, FACED scores, and NLR are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSurvival analysis\u003c/h2\u003e \u003cp\u003eAmong the 146 study patients, 42 (28.7%) died during the study period. Mortality varied according to BSI and FACED scores, from 20% and 22.22% in mild cases to 43.86% and 54.54% in severe cases. Using the NLR cut-off value of 2.76, mortality was 21.73% in those with NLR\u0026thinsp;\u0026lt;\u0026thinsp;2.76 and 35.06% in those with NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.078) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e(A) (B)\u003c/h3\u003e\n\u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eDeterminant factors of NLR\u003c/h3\u003e\n\u003cp\u003eThe results of the univariate Cox proportional hazards analysis are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. There tended to be a significant difference between mild and moderate BSI scores (hazard ratio\u0026thinsp;=\u0026thinsp;0.320, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.066). However, severe BSI scores were significantly different for survival rate (hazard ratio\u0026thinsp;=\u0026thinsp;0.386, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008) when compared with mild BSI scores. Regarding the FACED score, moderate cases showed a significant survival difference (hazard ratio\u0026thinsp;=\u0026thinsp;0.238, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) when compared with mild FACED scores. The severe group also tended to have a different survival rate compared with the mild group (hazard ratio\u0026thinsp;=\u0026thinsp;0.386, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.062). Patients with NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 demonstrated a higher death rate than those with NLR\u0026thinsp;\u0026lt;\u0026thinsp;2.76 (hazard ratio\u0026thinsp;=\u0026thinsp;0.514, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.078).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate Cox proportional hazard analysis of BSI, FACED scores, and NLR for mortality during study period\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBSI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSubjects, \u003cem\u003en\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMortality, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHazard ratio\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\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 \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (23.16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.320 (0.095\u0026ndash;1.078)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (43.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.386 (0.190\u0026ndash;0.783)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFACED\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (22.22%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (31.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.238 (0.09\u0026ndash;0.631)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (54.54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.386 (0.142\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNLR\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt; 2.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (21.73%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;2.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (35.06%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.514 (0.246\u0026ndash;1.077)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBSI: bronchiectasis severity index; NLR: neutrophil per lymphocyte ratio.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study demonstrate that the appropriate cut-off value of NLR was 2.76, and that NLR is associated with both disease severity (mild, moderate, and severe) and mortality in bronchiectasis patients. Several studies have proposed NLR threshold values that may be used to predict clinical severity, risk of exacerbation, and even mortality among patients with bronchiectasis. Kwok \u003cem\u003eet al\u003c/em\u003e. reported the appropriate thresholds to predict the need for hospitalization for bronchiectasis exacerbation during a 4-year follow-up\u003csup\u003e10\u003c/sup\u003e. Elevated NLR values have been reported in patients with positive sputum cultures and were also significantly higher in patients with bronchiectasis exacerbation when compared with healthy controls and correlates with clinical severity in bronchiectasis patients also exhibits good prognostic capacity for predicting future exacerbations\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Moreover, Nacaroglu \u003cem\u003eet al\u003c/em\u003e. demonstrated that NLR can be used as a biomarker to reflect chronic inflammation and acute exacerbations of bronchiectasis in children\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Our findings demonstrated that the BSI and FACED scores did not differ significantly between the groups. These results are consistent with previous reports, which also identified that BSI and FACED scores were not significantly correlated with NLR\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. However, in the current study, the survival rate in patients with severe BSI scores and moderate FACED scores differed significantly when compared with those with mild scores. Additionally, our previous study demonstrated that the distance\u0026ndash;saturation product (DSP) and lowest oxygen saturation during the 6-min walk test exhibited predictive power comparable to that of validated BSI and FACED scores in non-CF bronchiectasis patients\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. It should be emphasized that both the BSI and FACED scores incorporate forced expiratory volume in one second (FEV₁), which is closely associated with impaired gas exchange and obstructive pulmonary dysfunction. During exacerbations, neutrophils migrate to the airways and release neutrophil elastase and matrix metalloproteinases enzymes, which drive extracellular matrix degradation and epithelial injury, ultimately resulting in airway structural destruction. The consequent disruption promotes bacterial colonization and sustains a cycle of inflammation, tissue injury, and progressive bronchial dysfunction that contributes to the development and progression of bronchiectasis\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the present study, COPD prevalence was significantly higher in patients with NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76, whereas ICS use tended to be higher (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.051) compared with patients with NLR\u0026thinsp;\u0026lt;\u0026thinsp;2.76. Several studies have demonstrated that neutrophils have a strong relationship with COPD as a biomarker that can predict the effects of ICS in clinical practice, which are anti-inflammatory agents commonly prescribed for patients with COPD\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Although Sakurai \u003cem\u003eet al\u003c/em\u003e. demonstrated that NLR emerged as a predictor of exacerbations, one possible explanation is the relatively high rate of ICS prescription in their cohort compared with previous studies. Although ICS therapy is widely used, it may not adequately prevent exacerbations in COPD patients with elevated NLR\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMoreover, in the present study, we observed significantly different of current and past smokers, including greater smoking amounts (packs/year), in patients with NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76. This finding is not surprising, as prior evidence indicates that cigarette smoking exerts pro-inflammatory effects on the lungs even after smoking cessation in COPD patients\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. The persistent inflammatory response in the lungs, characterized by ongoing neutrophil recruitment and activation as previously described, contributes to the development and progression of emphysema and is closely associated with the severity of airflow limitation\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Furthermore, we observed significant differences in \u003cem\u003eP. aeruginosa\u003c/em\u003e isolation among the NLR groups. This is consistent with previous studies showing that NLR values were significantly different between patients with positive versus negative sputum cultures and were particularly elevated in those infected with \u003cem\u003eP. aeruginosa\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur study has several important limitations. First, as a retrospective study, the sample size was limited, underscoring the need for larger, prospective investigations. Second, all participants were recruited from a single center, which may restrict the generalizability of our findings. Third, the study was conducted during the COVID-19 pandemic, leading to loss of follow-up in some patients. Finally, larger multicenter studies with broader patient populations are required to validate and extend our results.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis retrospective study demonstrates that NLR is associated with non-cystic fibrosis bronchiectasis severity and mortality and may help predict survival rate. This information suggests that NLR and severity scoring systems may serve as potential predictors of clinical outcomes, being inexpensive and providing useful measures for assessing disease burden and prognosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Institutional Review Board of Chang Gung Memorial Hospital (Approval No. 202101879B0). All collected data were anonymized, stored in an encrypted database, and managed in compliance with patient privacy regulations. The need for informed consent was waived owing to the retrospective nature of the study and the lack of any intervention affecting patient care.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This study does not contain any individual person\u0026rsquo;s data in any \u003c/p\u003e\n\u003cp\u003eform including images or videos.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Available Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData available on request from the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not for profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors contributed to conception and design of the study. Meng-Heng Hsieh, Horng-Chyuan Lin and Jureeporn U-pathi: analyzed and interpreted the data. Meng-Heng Hsieh and Jureeporn U-pathi: drafted the manuscript. Meng-Heng Hsieh, Chiung-Hsin Chang, Chun-Yu Lin, Yueh-Fu Fang, Bing-Chen Wu, Mei-Yuan Teo, Hsin-I Cheng, and Tzu-Hsuan Chiu: provided the study materials, selected patients, collected and assembled data. All the authors draft the article or revising it critically for important intellectual content, have agreed on the journal to which the article has been submitted, approved the final manuscript and agreed to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the participants in the study also the investigators and members of the Department of Thoracic Medicine for their efforts. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFlume PA, Chalmers JD, Olivier KN. 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Particulate matter induces translocation of IL-6 from the lung to the systemic circulation. Am J Respir Cell Mol Biol. 2011;44(2):197\u0026ndash;204. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1165/rcmb.2009-0427OC\u003c/span\u003e\u003cspan address=\"10.1165/rcmb.2009-0427OC\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bronchiectasis, Neutrophil-to-lymphocyte ratio, Neutrophil, FACED Score, BSI Score","lastPublishedDoi":"10.21203/rs.3.rs-9071727/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9071727/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eWe aimed to evaluate the clinical relevance of the neutrophil-to-lymphocyte ratio (NLR) and the severity scoring systems in the potential diagnostic and prognostic value in stable non-CF bronchiectasis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study was conducted from 146 patients with stable non-CF bronchiectasis between January 2017 and August 2025. Participants were stratified into two groups based on the optimal AUC-derived NLR cut-off value of 2.76.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePatients with NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 had significantly higher proportions of current and former smokers (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031) and higher smoking amounts (packs/year) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031). The FEV1% was significantly higher in the NLR\u0026thinsp;\u0026lt;\u0026thinsp;2.76 group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021). The AUC between BSI, FACED and NLR were 0.716 vs. 0.706 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025) and 0.706 vs. 0.636 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032), respectively. Severe BSI scores were significantly different for survival rate (HR\u0026thinsp;=\u0026thinsp;0.386, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008). The moderate cases of FACED score showed a significant difference (HR\u0026thinsp;=\u0026thinsp;0.238, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) when compared with mild scores. NLR\u0026thinsp;\u0026ge;\u0026thinsp;2.76 patients demonstrated a higher death rate than NLR\u0026thinsp;\u0026lt;\u0026thinsp;2.76 (HR\u0026thinsp;=\u0026thinsp;0.514, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.078).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eNLR is associated with non-cystic fibrosis bronchiectasis severity and mortality and may help predict survival rate that may serve as potential predictors of clinical outcomes in stable non-CF bronchiectasis.\u003c/p\u003e","manuscriptTitle":"Peripheral Neutrophil-to-Lymphocyte Ratio in stable state Bronchiectasis as a Marker of Disease Severity: A Retrospective Cohort Study in North Taiwan","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-18 07:12:24","doi":"10.21203/rs.3.rs-9071727/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c18ab451-44ac-40f4-b866-886f07b906eb","owner":[],"postedDate":"March 18th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-06T06:11:09+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-18 07:12:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9071727","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9071727","identity":"rs-9071727","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}