The Role of Surgical Lung Biopsy in Diagnosis and Treatment Guidance for Interstitial Lung Diseases

The Role of Surgical Lung Biopsy in Diagnosis and Treatment Guidance for Interstitial Lung Diseases | 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 The Role of Surgical Lung Biopsy in Diagnosis and Treatment Guidance for Interstitial Lung Diseases Melike Ülker, Barış Demirkol, Ramazan Eren, Dilekhan Kizir, Celal Buğra Sezen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8961011/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 12 You are reading this latest preprint version Abstract Purpose Interstitial lung disease encompasses a wide range of conditions, with treatments tailored according to subgroup diagnoses. Surgical biopsy is recommended when a diagnosis cannot be established through clinical and radiological evaluations, or when the clinical course is uncertain. Methods Cases of surgical biopsy performed for interstitial lung disease from 2018 to 2023 were retrospectively analyzed. Postoperative complications, mortality rates, definitive diagnoses, and treatments were evaluated. Results Totally 253 patients were included in the study, comprising 150 males (59.3%) and 103 females (40.7%). The mean age was 58.4 ± 12.5 years. Minor complications were observed in 14 cases (5.5%), while major complications occurred in 7 (2.8%). Mortality was reported in two cases (0.8%) within the series. All patients who received a definitive diagnosis were initiated on disease-specific treatments. Medical treatment was initiated for 197 cases (77.8%). Specific treatment was started for 174 cases (68.8%) following the determination of an interstitial subgroup diagnosis. Conclusion Surgical biopsy performed via VATS is a safe procedure that provides significant therapeutic benefits by enabling a definitive diagnosis for patients with interstitial lung disease. Interstitial lung disease surgical biopsy VATS Figures Figure 1 Figure 2 Introduction Lung biopsy is recommended for patients with clinically undiagnosed conditions that suggest interstitial lung diseases, excluding idiopathic pulmonary fibrosis. Surgical biopsy is the most reliable method for definitive diagnosis in these undiagnosed patients following clinical, radiological, and bronchoscopic evaluations ( 1 ). Most previous studies showed that either an open lung biopsy with thoracotomy or video-assisted thoracoscopic surgery (VATS) approaches are appropriate for these patients for a definitive diagnosis. The outcomes of postoperative complications following surgical lung biopsy appear unclear. Although both procedures are often performed under general anesthesia, VATS lung biopsy has potential advantages compared to thoracotomy such as less postoperative pain and hospital stay, better cosmetic outcome, immune system and quality of life ( 2 , 3 ). In addition, morbidity and mortality rates are favorable in patients undergoing VAT procedures. The morbidity rate ranges between 5.8% and 14.7%, and the mortality rate varies between 1.4% and 4% ( 4 , 5 ). At the same time, in the study conducted by Richeldi et al, it was reported that the use of nintedanib and pirfenidone, which we call specific treatment, reduced the decrease in FVC by almost half when compared with the placebo group ( 6 ). We conducted a retrospective study to reveal out the clinicopathological features of patients who underwent surgical lung biopsy and analyzed the postoperative complications, morbidity and mortality rates for various diagnostic procedures. Methods Totally 253 patients underwent either mini-thoracotomy or video-thoracoscopy for definitive diagnosis of interstitial lung disease between 2018 and 2023 in our department. All patients underwent investigations for interstitial lung disease before the operation, including radiological imaging, bronchoscopy, and bronchoalveolar lavage, without any definitive diagnosis. We analyzed the clinicopathological features of the patients, including age, gender, smoking history, comorbidities, surgical procedures, histological examination, drainage time, postoperative complications, morbidity, mortality rates, and postoperative treatment. All patients presenting with various symptoms were requested to undergo high-resolution computed tomography (HRCT), spirometry (SFT), diffusing capacity for carbon monoxide (DLCO) testing, and connective tissue marker analysis. They were evaluated in an interstitial council with the participation of pulmonology, occupational diseases, and rheumatology specialists. Cases that could not be diagnosed following the council evaluation were further assessed by the pulmonology clinic using bronchoscopy, bronchoalveolar lavage, and cell counting analysis. Cases that remained undiagnosed after these interventional procedures were evaluated in a multidisciplinary council involving pulmonology, thoracic surgery, radiology, and pathology specialists. The side of the operation and the anatomical region for wedge resection were determined. In cases with widespread involvement, obtaining one sample each from the upper and lower lobes is our routine procedure. Cases with a thoracic tube in place for more than five days were classified as having prolonged air leakage. The surgical procedure was performed using uniportal/biportal VATS in 208 cases (82.2%), while a subxiphoid approach was applied in 37 cases (14.6%). Mini-thoracotomy was conducted in 8 cases (3.2%) due to extensive pleural adhesions. Surgical approach The patients were positioned in a lateral decubitus position and silicon soft pillows were used for patients in a comfortable position. First trocar access generally was placed at the eighth intercostal space along the midaxillary line for a 30-degree camera. The second trocar access which was a 1 cm skin incision was performed along the anterior and superior area from the camera port. The entry sites used for the uniportal or biportal technique were the same, while for the subxiphoid technique, an incision was made in the subxiphoid region. Radiologically and much more macroscopically, lung biopsies were performed as two wedge resections from upper and lower lobes. Resected specimens were taken out of the anterior port. A 24 or 28-ch chest tube was inserted from the lowest incision after hemostasis and aerostasis were carefully checked. At the end of the procedure, lung reexpansion was attained with the checking of thoracoscopic vision. Postoperative process In our clinical practice, surgical lung biopsy is deferred in patients who are experiencing an active exacerbation of their interstitial lung disease. Surgical intervention is planned in close collaboration with the pulmonology department and is scheduled only when deemed appropriate by the attending pulmonologists. In the postoperative period, if a patient experiences disease exacerbation, treatment decisions are made in coordination with pulmonologists to ensure individualized and optimal management. Following discharge, patients are referred back to the pulmonology department after the first postoperative surgical follow-up, provided that clinical and radiological evaluations are stable. Specific treatment is initiated according to the final pathological diagnosis. In our institutional algorithm, greater emphasis is placed on clinical trajectory rather than quantitative assessment of pulmonary function changes following surgery. Among patients who initiate specific therapy based on their pathological diagnosis, follow-up is conducted by pulmonology specialists, focusing on qualitative clinical parameters such as reduction in the number of exacerbations, improved six-minute walk distance, decreased oxygen requirement, and enhanced exercise tolerance. These patient-centered outcomes guide therapeutic adjustments more effectively than numeric pulmonary function parameters in routine practice. Medical treatment In this section, we tried to summarize our clinical treatment. The first and most important step in the treatment of hypersensitivity pneumonitis is removing the patient from exposure to the causative factor. For patients whose symptoms persist despite the removal of the causative factor or who exhibit severe symptoms, immunosuppressive therapies, primarily corticosteroids, are administered as the first line of treatment. For patients exhibiting a progressive fibrotic course despite immunosuppressive therapy, non-fibrotic treatments are preferred. In the treatment of Idiopathic Pulmonary Fibrosis (IPF), antifibrotic agents such as pirfenidone and nintedanib are used. Patients in advanced stages are referred for evaluation for lung transplantation. In patients diagnosed with Nonspecific Interstitial Pneumonia (NSIP), corticosteroids are initiated in cases where the inflammatory component is predominant, with additional immunosuppressive therapies administered if deemed necessary. In fibrotic NSIP cases, antifibrotic drugs are preferred for patients with a progressive fibrotic course, in addition to immunosuppressive therapy. In patients diagnosed with organizing pneumonia, etiological evaluation is conducted first, followed by the administration of corticosteroid therapy in most cases. Post-treatment, patients are monitored for the risk of recurrence. In the treatment of sarcoidosis, the therapeutic plan is tailored based on the stage and symptoms of the disease. In addition to inhaled steroid therapy, oral corticosteroids are initiated in patients with appropriate indications. For patients requiring long-term immunosuppressive therapy, alternative treatment options such as methotrexate and azathioprine are employed. In the treatment of cystic lung diseases, disease-specific therapeutic approaches are adopted. In the treatment of Pulmonary Langerhans Cell Histiocytosis (PLCH), smoking cessation is prioritized, and immunosuppressive agents are used in patients whose symptoms persist. For patients with Interstitial Pneumonia with Autoimmune Features (IPAF), immunosuppressive drugs are employed to suppress the immune response, with treatment plans individualized in collaboration with rheumatology support. The therapeutic approach for unclassifiable interstitial lung diseases requires a multidisciplinary evaluation. In managing these diseases, personalized treatment plans are developed by considering the severity of the patient’s clinical symptoms, lung function test results, and disease progression. In treatment selection, immunosuppressive therapy is preferred for cases suspected to be immune-mediated based on multidisciplinary evaluation, while antifibrotic therapies are employed in cases where fibrotic findings are predominant. For pulmonary malignancy cases, treatment options such as surgery, chemotherapy, or radiotherapy are determined based on the tumor type and stage following multidisciplinary evaluation in an oncology council. In patients with lung involvement due to rheumatological diseases, treatment is conducted under the supervision of the rheumatology department. Statistical Analysis While the data were analyzed retrospectively through patient files, there was no missing data from the patients in the study. Windows Office Excel 2020 and Word 2019 versions were used to create the database. IBM SPSS Statistics Version 26 program was used for statistical calculations. The descriptive results of the study are presented together with the corresponding percentages in the case of nominal or ordinal variables. Continuous variables are presented with mean and standard deviation values. "P" value below 0.05 was considered significant. The study was approved by the ethics/scientific committee of Tekirdag Dr. Ismail Fehmi Cumalıoglu City Hospital and was conducted by the principles of the Declaration of Helsinki by the number 91/2024. Results A total of 253 patients were included in the study, comprising 150 males (59.3%) and 103 females (40.7%). The mean age was 58.4 ± 12.5 years. Symptoms observed included shortness of breath in 225 cases (88.9%), cough in 128 cases (50.6%), chest discomfort in 13 cases (5.1%), sputum in 13 cases (5.1%), and hemoptysis in 1 case (0.4%), while 9 cases (3.6%) were asymptomatic. Of the cases, 175 (69.2%) were non-smokers. Among smokers, cigarette consumption averaged 28.7 ± 17.9 pack-years (range 5–100). Comorbidities included diabetes mellitus in 39 cases (15.4%), hypertension in 26 cases (10.3%), and coronary artery disease in 17 cases (6.7%). Preoperative FEV1 was 2.03 ± 0.76 liters (Range: 0.62–4.74), while preoperative FVC was 2.41 ± 0.88 liters (Range: 0.68–4.98). The demographic characteristics of the cases are presented in Table 1 . Table 1 Demographic characteristics of the patients Variables All patients 253 (%) Age ± SD (mean years) 58.4 ± 12.5 Male Female 150 (59.3) 103 (40.7) Non-smoker Ex smoker 175 (69.2) 78 (30.8) Smoking (pack/year) ± SD 28.7 ± 17.9 (R: 5-100) FVC (L) 2.41 ± 0.88 (R: 0.68–4.98) FEV1 (L) 2.03 ± 0.76 (R: 0.62–4.74) FEV1/FVC (%) 82.15 ± 15.22 (R: 36–118) Symptom None Hemoptysis Mucus Chest discomfort Cough Shortness of breath 9 (3.6) 1 (0.4) 13 (5.1) 13 (5.1) 128 (50.6) 225 (88.9) Comorbidity Diabetes Mellitus Hypertension Coronary Artery Disease Chronic Obstructive Pulmonary Disease History of Malignancy Rheumatological Disease Chronic Renal Failure 39 (15.4) 26 (10.3) 17 (6.7) 7 (2.8) 5 ( 2 ) 3 (1.2) 1 (0.4) SD: Standard deviation, R: Range, FVC: Forced vital capacity, FEV1: Forced expiratory volume in the first second The side of the operation was predominantly the right side in 203 cases (80.2%) and the left side in 50 cases (19.8%). The most common procedure performed was wedge resection from both the upper and lower lobes, applied in 204 cases (80.6%). In the preoperative evaluation using computed tomography, lymph node dissection was performed in 3 cases (1.2%) due to detected lymphadenopathy, and pleural biopsy was added in 2 cases (0.8%) due to pleural thickening or pleural irregularities. Other resection locations, as well as perioperative and postoperative variables, are shown in Table 2 . Table 2 Perioperative and postoperative outcomes Variables All patients 253 (%) Operation Side Right Left 203 (80.2) 50 (19.8) Operation technique VATS Subxiphoid Mini-thoracotomy 208 (82.2) 37 (14.6) 8 (3.2) Type of resection Upper-lower lobe wedge Lower lobe wedge Upper lobe wedge Lower-middle lobe wedge Upper-middle lobe wedge Upper-middle-lower lobe wedge Mediastinal lymph node dissection Pleural biopsy 204 (80.6) 16 (6.3) 14 (5.5) 13 (5.1) 3 (1.2) 3 (1.2) 3 (1.2) 2 (0.8) Complication 22 (8.7) Drainage time ± SD 2.9 ± 1.5 (Range: 1–15) Mortality (30-days) 2 (0.8) The mean drainage duration was 2.9 ± 1.5 days (Range: 1–15). Complications were observed in 22 cases (8.7%). Prolonged air leak was detected in 19 cases (7.5%), with five of these cases requiring additional drainage, while the remaining group was managed conservatively. One case underwent revision surgery due to hemorrhage, and ductus embolization was performed in one case due to chylothorax. Minor complications were observed in 14 cases (5.5%), while major complications occurred in 7 (2.8%). Mortality was reported in two cases (0.8%) during the study period. One patient was re-intubated due to hypoxia and respiratory failure and died of multiorgan failure. Another case died in the intensive care unit within the first 24 hours postoperatively due to myocardial infarction. No mortality was observed in patients who underwent the mini-thoracotomy procedure. Pathological examination of specimens revealed hypersensitivity pneumonitis as the most common diagnosis in 111 cases (43.9%), followed by idiopathic pulmonary fibrosis in 45 cases (17.8%). There was one case each of Churg-Strauss syndrome, Niemann-Pick disease, and Brit-Hoge-Dube syndrome. Images of the cases according to pathology diagnoses are shown in Fig. 1 and Fig. 2 . A definitive diagnosis could not be established in only 20 cases (7.9%). The definitive diagnosis rate was 92.1%. Other pathological classifications are detailed in Table 3 . All patients who received a definitive diagnosis were initiated on disease-specific treatments. Medical treatment aimed at diagnosis was initiated for 197 cases (77.8%), while remaning group was placed under follow-up. Specific treatments were started for 174 cases (68.8%) after the determination of an interstitial subgroup diagnosis. The treatment options included prednisone in 118 cases (46.6%), pirfenidone in 35 cases (13.8%), nintedanib in 23 cases (9.1%), and cellcept in 9 cases (3.6%). Table 3 Evaluation of Pathology Pathological Diagnosis Number of cases (n) Percentage of cases (%) Hypersensitivity pneumonitis 111 43.9 Idiopathic pulmonary fibrosis 45 17.8 Non-specific interstitial pneumonia 15 5.9 Usual interstitial pneumonia 4 1.6 Desquamative interstitial pneumonia 4 1.6 Organise pneumonia 5 2 Unclassifiable interstitial lung disease 8 3.2 Sarcoidosis 8 3.2 Cystic Lung Diseases* 7 2.8 Malignancy 6 2.4 Interstitial pneumonia with autoimmune features (IPAF) 4 1.6 Pleuroparenchymal fibroelastosis 4 1.6 Occupational lung diseases 3 1.2 Tuberculosis 2 0.8 Rheumatoid Arthritis 2 0.8 Churg Strauss Syndrome 1 0.4 Niemann Pick Syndrome 1 0.4 Pulmonary hypertension 1 0.4 Combined pulmonary fibrosis and emphysema 1 0.4 Idiopathic pulmonary fibrosis + Vasculitis 1 0.4 Non-specific group 20 7.9 *Cystic lung diseases include Brit-Hoge-Dube syndrome, lymphangiomatosis and pulmonary langerhans cell histiocytosis Discussion Interstitial lung disease is a broad-spectrum condition for which different treatments are applied based on subgroup diagnoses. Surgical biopsy plays a critical role in cases where clinical and radiological evaluations fail to establish a diagnosis or when the clinical course raises suspicion. While cryobiopsy has a high diagnostic yield, it has been available and actively used in our clinic since 2020. In a study conducted by Turan and colleagues in the pulmonary diseases department of our hospital, the diagnostic accuracy of transbronchial cryobiopsy was 66.6% based on pathology and 74.1% following multidisciplinary council evaluation ( 7 ). In the study conducted by Lieberman et al. in 2017, 47 cases were evaluated, reporting a minor complication rate of 21.3%, a major complication rate of 6.4%, and a mortality rate of 8.5% ( 8 ). In our study, the minor complication rate was 5.5%, the major complication rate was 2.8%, and the mortality rate was 0.8%. Compared to this study, our complication and mortality rates are lower. This study recommends performing a surgical biopsy in the early stages of the disease, typically when there is no widespread lung involvement and symptoms are mild to moderate. In our clinic, cases in the exacerbation phase are not subjected to surgical biopsy. In the study by Lieberman et al., the evaluation of computed tomography scans by a thoracic radiologist showed only 60.5% concordance with the final pathological diagnosis. Among cases evaluated in a multidisciplinary council based on biopsy results, a definitive diagnosis could be established, and treatment changes were made in 51.1% of cases. One of the diagnostic groups of particular importance includes malignancy cases. In the study by Lieberman et al., 4.3% of cases were diagnosed with malignancy, whereas in our study, the malignancy diagnosis rate was 2.4%. The accurate diagnosis and treatment guidance of previously undiagnosed malignancy cases remain a critical aspect of care. In the study conducted by Durheim et al. in 2017, data from The Society of Thoracic Surgeons database was utilized, and 3,085 cases were analyzed. Postoperative respiratory distress was observed in 2.9% of cases in the study, with a mortality rate of 1.5% ( 9 ). In our study, respiratory failure was observed in one case (0.4%), which resulted in mortality. The study highlighted that preoperative corticosteroid use was identified as a risk factor for mortality. In our study, preoperative corticosteroid use was minimal, as most cases lacked a definitive diagnosis before surgery. In the study conducted by Nguyen and Meyer, a literature review revealed that the minor complication rate was 18.2% for open biopsy and 9.6% for VATS biopsy, while mortality rates were 4.3% for open biopsy and 2.1% for VATS biopsy ( 10 ). In our study, both complication and mortality rates were lower than these figures, with the VATS technique being utilized in our clinic. Due to severe pleural adhesions, mini-thoracotomy was performed in 8 cases (3.2%), with partial pneumolysis carried out to create a resectable area. No mortality was observed in the mini-thoracotomy group. In the study conducted by Otsuka et al., in 2022, 129 cases were analyzed and 26.4% of the cases could not be classified based on their pathological diagnoses and were categorized as unclassifiable idiopathic interstitial pneumonia As the number of biopsies performed on the same case increases, the rate of achieving a surgical diagnosis also rises; however, this also creates a predisposition for complications. While this study reported a rate of 9% for biopsies performed from three different lobes, in our study, this was done in 3% of cases. In the study by Otsuka et al., the complication rate was found to be 10.1%, while no mortality was observed. Resections performed from the apical portion of segment S1 in the upper lobe showed an increased incidence of postoperative pneumothorax compared to other upper lobe segments, while no increased risk was observed in wedge resections performed in the lower lobes ( 11 ). In our clinic, the apical region is generally not used as a procedure. In a meta-analysis conducted by Han et al., 2,148 cases from 23 studies were evaluated, and the median rate of diagnosis through surgical biopsy was reported as 95%. The diagnostic rate ranged from 42% to 100%, with only one study reporting a rate below 70%. When comparing six studies that applied both VATS and open surgery, no significant difference was observed in the determination of the pathological diagnosis. In the pathological specimen evaluation, idiopathic pulmonary fibrosis was the most common diagnosis at 33.5%, followed by NSIP at 11.9% and HP at 9.6% ( 12 ). In our study, the rate of definitive diagnosis was 92.1%, and the most common diagnosis in the pathological specimen evaluation was hypersensitivity pneumonitis at 43.9%, followed by idiopathic pulmonary fibrosis at 17.8%. In the study conducted by Fibla et al., 311 cases underwent surgical biopsy, and 74.6% achieved a specific, definitive diagnosis. The most common diagnoses were idiopathic pulmonary fibrosis at 39% and cryptogenic organizing pneumonia at 10%. In the cases, 77% started a new treatment, 40.7% had a change in the treatment strategy, and 6.8% discontinued the previous treatment. In our study, 77.8% of cases started medical treatment, while 68.8% of cases in the IAH subgroups began specific treatment. ( 13 ). It is evident that these studies provided therapeutic benefits for the disease through definitive diagnosis. After clinical and radiological evaluation, the diagnostic rates through bronchoscopy and transbronchial cryobiopsy are high, and typical UIP cases in smokers can receive a diagnosis. In the pathology review of our study, hypersensitivity pneumonia was the most commonly observed condition, along with specific and rare subdiagnoses, indicating that the cases referred for surgery were optimally selected. Being a specialized center in pulmonology and thoracic surgery, and a tertiary hospital, with extended procedures being performed and a high annual patient intervention rate, this is an experienced institution. It is crucial to plan the diagnosis and treatment of specialized groups, such as interstitial lung diseases, through a multidisciplinary approach. Limitation Transbronchial cryobiopsy has been actively used in our clinic in recent years. However, during the course of the study, it was not used equally throughout the periods due to technical issues. Although all patients who underwent surgical lung biopsy were included in the study, the total number of patients evaluated for interstitial lung disease during this process is unknown. This study included a heterogeneous group of interstitial lung disease subtypes diagnosed through surgical biopsy. Although our center is a national reference unit with high procedural volume, the diversity of diagnoses limited standardized follow-up of pulmonary function across subgroups. Additionally, a prospective protocol for systematic pre- and post-biopsy pulmonary function testing was not implemented during the study period. Future studies focusing on specific diagnostic subgroups with structured functional follow-up are needed to better understand the impact of surgical lung biopsy on respiratory function. Conclusion Surgical lung biopsy is recommended for unclassified ILD, clinical high-resolution CT or transbronchial lung biopsy groups that cannot be classified. It can be said that surgical biopsy with VATS can be performed safely and provides a significant therapeutic benefit in this patient group. It remains the gold standard in the diagnosis of ILD due to its high rate of definitive diagnosis. Declarations Conflict of interest: The authors declare that there is no conflict of interest. Ethics Committee Approval The study was approved by the ethics/scientific committee of Tekirdag Dr. Ismail Fehmi Cumalıoglu City Hospital and was conducted by the principles of the Declaration of Helsinki by the number 91/2024. A written informed consent was obtained from each patient Consent for Publication: Consent for publication of identifying images or other personal or clinical details of the participants has been obtained. Data Sharing Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. Funding: This research did not receive any specific grant from any funding agencies. Author Contribution Author Contributions: Conceptualization: MÜ, BDData curation: MÜ, DK, REFormal analysis: MÜFunding acquisition: VEInvestigation: MÜ, BD, EÇMethodology: MÜ, EÇ, MMProject administration: MÜResources: MÜ, CBSSoftware: MÜSupervision: MM, EÇValidation: MÜWriting-original draft: MÜ, EÇWriting-review&editing: MÜ Acknowledgment: None Data Availability The data that support the findings of this study are available from the corresponding author upon reasonable request. References Hunninghake GW, Zimmerman MB, Schwartz DA, King TE, Lynch J, Hegele R. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2001;164:193–6. Khalil M, Cowen M, Chaudhry M, Loubani M. Single versus multiple lung biopsies for suspected interstitial lung disease. Asian Cardiovasc Thorac Annals 2016, 24(8) 788–91. Sedrakyan A, van der Meulen J, Lewsey J, Treasure T. Video-assisted thoracic surgery of treatment of pneumothorax and lung resections: systematic review of randomized clinical trials. BMJ. 2004;329:1008–10. Zhang D, Liu Y. Surgical lung biopsies in 418 patients with suspected interstitial lung disease in China. Intern Med. 2010;49:1097–102. Park JH, Kim DK, Kim DS, Koh Y, Lee S, Kim WS, et al. Mortality and risk factors for surgical lung biopsy in patient with idiopathic interstitial pneumonia. Eur J Cardiothorac Surg. 2007;31:1115–9. Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet. 2017;389:1941–52. Turan D, Uğur Chousein EG, Koç AS, Çörtük M, Yıldırım Z, Demirkol B, et al. Transbronchial cryobiopsy for diagnosing parenchymal lung diseases: real-life experience from a tertiary referral center. Sarcoidosis Vasc Diffuse Lung Dis. 2021;38(1):e2021004. Lieberman S, Gleason JB, İlyas MIM, Martinez F, Mehta J, Savage EB. Assessing the safety and clinical impact of thoracoscopic lung biopsy in patients with interstitial lung disease. J Clin Diagn Res. 2017 Mar,Vol-11(3):57–9. Durheim MT, Kim S, Gulack BC, Burfeind WR, Gaissert H, Kosinski AS, et al. Mortality and respiratory failure after thoracoscopic lung biopsy for interstitial lung disease. Ann Thorac Surg. 2017;104(2):465–70. Nguyen W, Meyer KC. Surgical lung biopsy for the diagnosis of interstitial lung disease: a review of the literature and recommendations for optimizing safety and efficacy. Sarcoidosis Vasc Diffuse Lung Dis. 2013;30:3–16. Otsuka H, Sano A, Azuma Y, Sakai T, Koezuka S, Sugino K, et al. Surgical lung biopsy for interstitial lung diseases: a single center study of 129 patients. J Thorac Dis. 2022;14(6):1972–9. Han Q, Luo Q, Xie JX, Wu L, Liao L, Zhang X, et al. Diagnostic yield and postoperative mortality associated with surgical lung biopsy for evaluation of interstitial lung diseases: A systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2015;149:1394–401. Fibla JJ, Brunelli A, Cassivi SD, Deschamps C. Aggregate risk score for predicting mortality after surgical biopsy for interstitial lung disease. Interact Cardiovasc Thorac Surg. 2012;15(2):276–79. Additional Declarations No competing interests reported. Supplementary Files Graphicalabstractimage.png Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 12 May, 2026 Reviews received at journal 11 May, 2026 Reviewers agreed at journal 11 May, 2026 Reviews received at journal 07 May, 2026 Reviews received at journal 06 May, 2026 Reviewers agreed at journal 06 May, 2026 Reviewers agreed at journal 04 May, 2026 Reviewers invited by journal 04 May, 2026 Editor invited by journal 04 May, 2026 Editor assigned by journal 04 Mar, 2026 Submission checks completed at journal 28 Feb, 2026 First submitted to journal 28 Feb, 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-8961011","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":638398029,"identity":"84a6f717-6941-4c8f-820e-eb354ded8438","order_by":0,"name":"Melike Ülker","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIie3QsYrCMBjA8YTATdGuucFHcCoUhPgkLpZCb+ruUCRd4lJxrfgS3nLcaAj0loJrNy2+gOLkIn7RcxHarg75D2kb+uNLi5DN9pYRoQRcuhSWk7lDONk0E/wgH0DwUiBmdloJfhLSuROEGkl/liQqmyBfUp2fh7982p9pmBLzUR3xCiXUugDSkcEqKkLmFT6QPIxEHSl9oSoJxKEuiaRm3gYIFrqe7CogV0OcMxkYsq1aSAl/7FuYg6WEYEPKtilwcpXlzJU0d/Fchp8/JUwZN33Ln9anNOa9BQ0O6CK5422/qv0x5rXkP/byPG5+3Waz2Wwt3QBmemasJUexZAAAAABJRU5ErkJggg==","orcid":"","institution":"Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital","correspondingAuthor":true,"prefix":"","firstName":"Melike","middleName":"","lastName":"Ülker","suffix":""},{"id":638398030,"identity":"da7ba547-7772-4dc2-acff-0de36c33a38a","order_by":1,"name":"Barış Demirkol","email":"","orcid":"","institution":"Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Barış","middleName":"","lastName":"Demirkol","suffix":""},{"id":638398032,"identity":"23d3d384-0f01-419f-9392-13d7e8e354dd","order_by":2,"name":"Ramazan Eren","email":"","orcid":"","institution":"Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ramazan","middleName":"","lastName":"Eren","suffix":""},{"id":638398034,"identity":"6daa7f01-7b81-435b-9662-fd6ead525559","order_by":3,"name":"Dilekhan Kizir","email":"","orcid":"","institution":"Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dilekhan","middleName":"","lastName":"Kizir","suffix":""},{"id":638398035,"identity":"21f683ea-ca1a-4110-a4c4-3b62a073722e","order_by":4,"name":"Celal Buğra Sezen","email":"","orcid":"","institution":"Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Celal","middleName":"Buğra","lastName":"Sezen","suffix":""},{"id":638398039,"identity":"1ccde3ad-a7ca-4157-af10-88e0ad1c1750","order_by":5,"name":"Volkan Erdoğu","email":"","orcid":"","institution":"Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Volkan","middleName":"","lastName":"Erdoğu","suffix":""},{"id":638398042,"identity":"432aa6a0-1ed2-4971-8acb-ee9491273729","order_by":6,"name":"Muzaffer Metin","email":"","orcid":"","institution":"Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Muzaffer","middleName":"","lastName":"Metin","suffix":""},{"id":638398043,"identity":"961168cf-c191-470d-8651-b75c8f88ae8f","order_by":7,"name":"Erdoğan Çetinkaya","email":"","orcid":"","institution":"Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Erdoğan","middleName":"","lastName":"Çetinkaya","suffix":""}],"badges":[],"createdAt":"2026-02-24 20:54:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8961011/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8961011/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109150448,"identity":"93e29e1e-b7ff-4b1d-8f66-c4954dc2375d","added_by":"auto","created_at":"2026-05-13 05:28:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":231373,"visible":true,"origin":"","legend":"\u003cp\u003eImages according to pathology diagnoses 1\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8961011/v1/30dd2975672612b21cd533a5.png"},{"id":109150449,"identity":"c89302b6-70d0-446e-9b4a-dfdb2db53945","added_by":"auto","created_at":"2026-05-13 05:28:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":308807,"visible":true,"origin":"","legend":"\u003cp\u003eImages according to pathology diagnoses 2\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8961011/v1/ed3383952229ab8988c30abc.png"},{"id":109207996,"identity":"6fc7285d-11b9-49bc-99fe-c944eb188f47","added_by":"auto","created_at":"2026-05-13 15:22:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":777312,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8961011/v1/b699a598-b7cd-4119-82b9-989a5f1e917a.pdf"},{"id":109205352,"identity":"20d5832f-2c0c-4f30-bc75-da1fb9e99ad7","added_by":"auto","created_at":"2026-05-13 15:04:22","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":446469,"visible":true,"origin":"","legend":"","description":"","filename":"Graphicalabstractimage.png","url":"https://assets-eu.researchsquare.com/files/rs-8961011/v1/9d97d1aafd31c87ca9e265e1.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Role of Surgical Lung Biopsy in Diagnosis and Treatment Guidance for Interstitial Lung Diseases","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLung biopsy is recommended for patients with clinically undiagnosed conditions that suggest interstitial lung diseases, excluding idiopathic pulmonary fibrosis. Surgical biopsy is the most reliable method for definitive diagnosis in these undiagnosed patients following clinical, radiological, and bronchoscopic evaluations (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMost previous studies showed that either an open lung biopsy with thoracotomy or video-assisted thoracoscopic surgery (VATS) approaches are appropriate for these patients for a definitive diagnosis. The outcomes of postoperative complications following surgical lung biopsy appear unclear. Although both procedures are often performed under general anesthesia, VATS lung biopsy has potential advantages compared to thoracotomy such as less postoperative pain and hospital stay, better cosmetic outcome, immune system and quality of life (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In addition, morbidity and mortality rates are favorable in patients undergoing VAT procedures. The morbidity rate ranges between 5.8% and 14.7%, and the mortality rate varies between 1.4% and 4% (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAt the same time, in the study conducted by Richeldi et al, it was reported that the use of nintedanib and pirfenidone, which we call specific treatment, reduced the decrease in FVC by almost half when compared with the placebo group (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWe conducted a retrospective study to reveal out the clinicopathological features of patients who underwent surgical lung biopsy and analyzed the postoperative complications, morbidity and mortality rates for various diagnostic procedures.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eTotally 253 patients underwent either mini-thoracotomy or video-thoracoscopy for definitive diagnosis of interstitial lung disease between 2018 and 2023 in our department. All patients underwent investigations for interstitial lung disease before the operation, including radiological imaging, bronchoscopy, and bronchoalveolar lavage, without any definitive diagnosis.\u003c/p\u003e \u003cp\u003eWe analyzed the clinicopathological features of the patients, including age, gender, smoking history, comorbidities, surgical procedures, histological examination, drainage time, postoperative complications, morbidity, mortality rates, and postoperative treatment.\u003c/p\u003e \u003cp\u003eAll patients presenting with various symptoms were requested to undergo high-resolution computed tomography (HRCT), spirometry (SFT), diffusing capacity for carbon monoxide (DLCO) testing, and connective tissue marker analysis. They were evaluated in an interstitial council with the participation of pulmonology, occupational diseases, and rheumatology specialists. Cases that could not be diagnosed following the council evaluation were further assessed by the pulmonology clinic using bronchoscopy, bronchoalveolar lavage, and cell counting analysis. Cases that remained undiagnosed after these interventional procedures were evaluated in a multidisciplinary council involving pulmonology, thoracic surgery, radiology, and pathology specialists. The side of the operation and the anatomical region for wedge resection were determined. In cases with widespread involvement, obtaining one sample each from the upper and lower lobes is our routine procedure. Cases with a thoracic tube in place for more than five days were classified as having prolonged air leakage.\u003c/p\u003e \u003cp\u003eThe surgical procedure was performed using uniportal/biportal VATS in 208 cases (82.2%), while a subxiphoid approach was applied in 37 cases (14.6%). Mini-thoracotomy was conducted in 8 cases (3.2%) due to extensive pleural adhesions.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSurgical approach\u003c/h2\u003e \u003cp\u003eThe patients were positioned in a lateral decubitus position and silicon soft pillows were used for patients in a comfortable position. First trocar access generally was placed at the eighth intercostal space along the midaxillary line for a 30-degree camera. The second trocar access which was a 1 cm skin incision was performed along the anterior and superior area from the camera port. The entry sites used for the uniportal or biportal technique were the same, while for the subxiphoid technique, an incision was made in the subxiphoid region. Radiologically and much more macroscopically, lung biopsies were performed as two wedge resections from upper and lower lobes. Resected specimens were taken out of the anterior port. A 24 or 28-ch chest tube was inserted from the lowest incision after hemostasis and aerostasis were carefully checked. At the end of the procedure, lung reexpansion was attained with the checking of thoracoscopic vision.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePostoperative process\u003c/h3\u003e\n\u003cp\u003eIn our clinical practice, surgical lung biopsy is deferred in patients who are experiencing an active exacerbation of their interstitial lung disease. Surgical intervention is planned in close collaboration with the pulmonology department and is scheduled only when deemed appropriate by the attending pulmonologists. In the postoperative period, if a patient experiences disease exacerbation, treatment decisions are made in coordination with pulmonologists to ensure individualized and optimal management.\u003c/p\u003e \u003cp\u003eFollowing discharge, patients are referred back to the pulmonology department after the first postoperative surgical follow-up, provided that clinical and radiological evaluations are stable. Specific treatment is initiated according to the final pathological diagnosis. In our institutional algorithm, greater emphasis is placed on clinical trajectory rather than quantitative assessment of pulmonary function changes following surgery.\u003c/p\u003e \u003cp\u003eAmong patients who initiate specific therapy based on their pathological diagnosis, follow-up is conducted by pulmonology specialists, focusing on qualitative clinical parameters such as reduction in the number of exacerbations, improved six-minute walk distance, decreased oxygen requirement, and enhanced exercise tolerance. These patient-centered outcomes guide therapeutic adjustments more effectively than numeric pulmonary function parameters in routine practice.\u003c/p\u003e\n\u003ch3\u003eMedical treatment\u003c/h3\u003e\n\u003cp\u003eIn this section, we tried to summarize our clinical treatment. The first and most important step in the treatment of hypersensitivity pneumonitis is removing the patient from exposure to the causative factor. For patients whose symptoms persist despite the removal of the causative factor or who exhibit severe symptoms, immunosuppressive therapies, primarily corticosteroids, are administered as the first line of treatment. For patients exhibiting a progressive fibrotic course despite immunosuppressive therapy, non-fibrotic treatments are preferred.\u003c/p\u003e \u003cp\u003eIn the treatment of Idiopathic Pulmonary Fibrosis (IPF), antifibrotic agents such as pirfenidone and nintedanib are used. Patients in advanced stages are referred for evaluation for lung transplantation. In patients diagnosed with Nonspecific Interstitial Pneumonia (NSIP), corticosteroids are initiated in cases where the inflammatory component is predominant, with additional immunosuppressive therapies administered if deemed necessary. In fibrotic NSIP cases, antifibrotic drugs are preferred for patients with a progressive fibrotic course, in addition to immunosuppressive therapy.\u003c/p\u003e \u003cp\u003eIn patients diagnosed with organizing pneumonia, etiological evaluation is conducted first, followed by the administration of corticosteroid therapy in most cases. Post-treatment, patients are monitored for the risk of recurrence. In the treatment of sarcoidosis, the therapeutic plan is tailored based on the stage and symptoms of the disease. In addition to inhaled steroid therapy, oral corticosteroids are initiated in patients with appropriate indications. For patients requiring long-term immunosuppressive therapy, alternative treatment options such as methotrexate and azathioprine are employed.\u003c/p\u003e \u003cp\u003eIn the treatment of cystic lung diseases, disease-specific therapeutic approaches are adopted. In the treatment of Pulmonary Langerhans Cell Histiocytosis (PLCH), smoking cessation is prioritized, and immunosuppressive agents are used in patients whose symptoms persist. For patients with Interstitial Pneumonia with Autoimmune Features (IPAF), immunosuppressive drugs are employed to suppress the immune response, with treatment plans individualized in collaboration with rheumatology support.\u003c/p\u003e \u003cp\u003eThe therapeutic approach for unclassifiable interstitial lung diseases requires a multidisciplinary evaluation. In managing these diseases, personalized treatment plans are developed by considering the severity of the patient\u0026rsquo;s clinical symptoms, lung function test results, and disease progression. In treatment selection, immunosuppressive therapy is preferred for cases suspected to be immune-mediated based on multidisciplinary evaluation, while antifibrotic therapies are employed in cases where fibrotic findings are predominant.\u003c/p\u003e \u003cp\u003eFor pulmonary malignancy cases, treatment options such as surgery, chemotherapy, or radiotherapy are determined based on the tumor type and stage following multidisciplinary evaluation in an oncology council. In patients with lung involvement due to rheumatological diseases, treatment is conducted under the supervision of the rheumatology department.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eWhile the data were analyzed retrospectively through patient files, there was no missing data from the patients in the study. Windows Office Excel 2020 and Word 2019 versions were used to create the database. IBM SPSS Statistics Version 26 program was used for statistical calculations. The descriptive results of the study are presented together with the corresponding percentages in the case of nominal or ordinal variables. Continuous variables are presented with mean and standard deviation values. \"P\" value below 0.05 was considered significant.\u003c/p\u003e \u003cp\u003e The study was approved by the ethics/scientific committee of Tekirdag Dr. Ismail Fehmi Cumalıoglu City Hospital and was conducted by the principles of the Declaration of Helsinki by the number 91/2024.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 253 patients were included in the study, comprising 150 males (59.3%) and 103 females (40.7%). The mean age was 58.4\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5 years. Symptoms observed included shortness of breath in 225 cases (88.9%), cough in 128 cases (50.6%), chest discomfort in 13 cases (5.1%), sputum in 13 cases (5.1%), and hemoptysis in 1 case (0.4%), while 9 cases (3.6%) were asymptomatic. Of the cases, 175 (69.2%) were non-smokers. Among smokers, cigarette consumption averaged 28.7\u0026thinsp;\u0026plusmn;\u0026thinsp;17.9 pack-years (range 5\u0026ndash;100).\u003c/p\u003e \u003cp\u003eComorbidities included diabetes mellitus in 39 cases (15.4%), hypertension in 26 cases (10.3%), and coronary artery disease in 17 cases (6.7%). Preoperative FEV1 was 2.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76 liters (Range: 0.62\u0026ndash;4.74), while preoperative FVC was 2.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88 liters (Range: 0.68\u0026ndash;4.98). The demographic characteristics of the cases are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\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 \u003cp\u003eDemographic characteristics of the patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients 253 (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (mean years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58.4\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150 (59.3)\u003c/p\u003e \u003cp\u003e103 (40.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-smoker\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eEx smoker\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e175 (69.2)\u003c/p\u003e \u003cp\u003e78 (30.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmoking (pack/year)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.7\u0026thinsp;\u0026plusmn;\u0026thinsp;17.9 (R: 5-100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFVC (L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88 (R: 0.68\u0026ndash;4.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV1 (L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76 (R: 0.62\u0026ndash;4.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFEV1/FVC (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.15 \u0026plusmn; 15.22 (R: 36\u0026ndash;118)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSymptom\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eNone\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eHemoptysis\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eMucus\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eChest discomfort\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eCough\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eShortness of breath\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (3.6)\u003c/p\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003cp\u003e13 (5.1)\u003c/p\u003e \u003cp\u003e13 (5.1)\u003c/p\u003e \u003cp\u003e128 (50.6)\u003c/p\u003e \u003cp\u003e225 (88.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidity\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eDiabetes Mellitus\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eHypertension\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eCoronary Artery Disease\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eChronic Obstructive Pulmonary Disease\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eHistory of Malignancy\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eRheumatological Disease\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eChronic Renal Failure\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (15.4)\u003c/p\u003e \u003cp\u003e26 (10.3)\u003c/p\u003e \u003cp\u003e17 (6.7)\u003c/p\u003e \u003cp\u003e7 (2.8)\u003c/p\u003e \u003cp\u003e5 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e3 (1.2)\u003c/p\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSD: Standard deviation, R: Range, FVC: Forced vital capacity,\u003c/p\u003e \u003cp\u003eFEV1: Forced expiratory volume in the first second\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\u003eThe side of the operation was predominantly the right side in 203 cases (80.2%) and the left side in 50 cases (19.8%). The most common procedure performed was wedge resection from both the upper and lower lobes, applied in 204 cases (80.6%). In the preoperative evaluation using computed tomography, lymph node dissection was performed in 3 cases (1.2%) due to detected lymphadenopathy, and pleural biopsy was added in 2 cases (0.8%) due to pleural thickening or pleural irregularities. Other resection locations, as well as perioperative and postoperative variables, are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\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\u003ePerioperative and postoperative outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients 253 (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperation Side\u003c/p\u003e \u003cp\u003eRight\u003c/p\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e203 (80.2)\u003c/p\u003e \u003cp\u003e50 (19.8)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperation technique\u003c/p\u003e \u003cp\u003eVATS\u003c/p\u003e \u003cp\u003eSubxiphoid\u003c/p\u003e \u003cp\u003eMini-thoracotomy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e208 (82.2)\u003c/p\u003e \u003cp\u003e37 (14.6)\u003c/p\u003e \u003cp\u003e8 (3.2)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of resection\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eUpper-lower lobe wedge\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eLower lobe wedge\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eUpper lobe wedge\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eLower-middle lobe wedge\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eUpper-middle lobe wedge\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eUpper-middle-lower lobe wedge\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eMediastinal lymph node dissection\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003ePleural biopsy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e204 (80.6)\u003c/p\u003e \u003cp\u003e16 (6.3)\u003c/p\u003e \u003cp\u003e14 (5.5)\u003c/p\u003e \u003cp\u003e13 (5.1)\u003c/p\u003e \u003cp\u003e3 (1.2)\u003c/p\u003e \u003cp\u003e3 (1.2)\u003c/p\u003e \u003cp\u003e3 (1.2)\u003c/p\u003e \u003cp\u003e2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplication\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (8.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDrainage time\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 (Range: 1\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMortality (30-days)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.8)\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\u003eThe mean drainage duration was 2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 days (Range: 1\u0026ndash;15). Complications were observed in 22 cases (8.7%). Prolonged air leak was detected in 19 cases (7.5%), with five of these cases requiring additional drainage, while the remaining group was managed conservatively. One case underwent revision surgery due to hemorrhage, and ductus embolization was performed in one case due to chylothorax. Minor complications were observed in 14 cases (5.5%), while major complications occurred in 7 (2.8%). Mortality was reported in two cases (0.8%) during the study period. One patient was re-intubated due to hypoxia and respiratory failure and died of multiorgan failure. Another case died in the intensive care unit within the first 24 hours postoperatively due to myocardial infarction. No mortality was observed in patients who underwent the mini-thoracotomy procedure.\u003c/p\u003e \u003cp\u003ePathological examination of specimens revealed hypersensitivity pneumonitis as the most common diagnosis in 111 cases (43.9%), followed by idiopathic pulmonary fibrosis in 45 cases (17.8%). There was one case each of Churg-Strauss syndrome, Niemann-Pick disease, and Brit-Hoge-Dube syndrome. Images of the cases according to pathology diagnoses are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. A definitive diagnosis could not be established in only 20 cases (7.9%). The definitive diagnosis rate was 92.1%. Other pathological classifications are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. All patients who received a definitive diagnosis were initiated on disease-specific treatments. Medical treatment aimed at diagnosis was initiated for 197 cases (77.8%), while remaning group was placed under follow-up. Specific treatments were started for 174 cases (68.8%) after the determination of an interstitial subgroup diagnosis. The treatment options included prednisone in 118 cases (46.6%), pirfenidone in 35 cases (13.8%), nintedanib in 23 cases (9.1%), and cellcept in 9 cases (3.6%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \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\u003eEvaluation of Pathology\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological Diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of cases (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercentage of cases (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypersensitivity pneumonitis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIdiopathic pulmonary fibrosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-specific interstitial pneumonia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUsual interstitial pneumonia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDesquamative interstitial pneumonia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOrganise pneumonia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUnclassifiable interstitial lung disease\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSarcoidosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCystic Lung Diseases*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMalignancy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInterstitial pneumonia with autoimmune features (IPAF)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePleuroparenchymal fibroelastosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOccupational lung diseases\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTuberculosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRheumatoid Arthritis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChurg Strauss Syndrome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNiemann Pick Syndrome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePulmonary hypertension\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCombined pulmonary fibrosis and emphysema\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIdiopathic pulmonary fibrosis\u0026thinsp;+\u0026thinsp;Vasculitis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-specific group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e*Cystic lung diseases include Brit-Hoge-Dube syndrome, lymphangiomatosis and pulmonary langerhans cell histiocytosis\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eInterstitial lung disease is a broad-spectrum condition for which different treatments are applied based on subgroup diagnoses. Surgical biopsy plays a critical role in cases where clinical and radiological evaluations fail to establish a diagnosis or when the clinical course raises suspicion. While cryobiopsy has a high diagnostic yield, it has been available and actively used in our clinic since 2020. In a study conducted by Turan and colleagues in the pulmonary diseases department of our hospital, the diagnostic accuracy of transbronchial cryobiopsy was 66.6% based on pathology and 74.1% following multidisciplinary council evaluation (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the study conducted by Lieberman et al. in 2017, 47 cases were evaluated, reporting a minor complication rate of 21.3%, a major complication rate of 6.4%, and a mortality rate of 8.5% (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In our study, the minor complication rate was 5.5%, the major complication rate was 2.8%, and the mortality rate was 0.8%. Compared to this study, our complication and mortality rates are lower. This study recommends performing a surgical biopsy in the early stages of the disease, typically when there is no widespread lung involvement and symptoms are mild to moderate. In our clinic, cases in the exacerbation phase are not subjected to surgical biopsy. In the study by Lieberman et al., the evaluation of computed tomography scans by a thoracic radiologist showed only 60.5% concordance with the final pathological diagnosis. Among cases evaluated in a multidisciplinary council based on biopsy results, a definitive diagnosis could be established, and treatment changes were made in 51.1% of cases. One of the diagnostic groups of particular importance includes malignancy cases. In the study by Lieberman et al., 4.3% of cases were diagnosed with malignancy, whereas in our study, the malignancy diagnosis rate was 2.4%. The accurate diagnosis and treatment guidance of previously undiagnosed malignancy cases remain a critical aspect of care.\u003c/p\u003e \u003cp\u003eIn the study conducted by Durheim et al. in 2017, data from The Society of Thoracic Surgeons database was utilized, and 3,085 cases were analyzed. Postoperative respiratory distress was observed in 2.9% of cases in the study, with a mortality rate of 1.5% (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In our study, respiratory failure was observed in one case (0.4%), which resulted in mortality. The study highlighted that preoperative corticosteroid use was identified as a risk factor for mortality. In our study, preoperative corticosteroid use was minimal, as most cases lacked a definitive diagnosis before surgery.\u003c/p\u003e \u003cp\u003eIn the study conducted by Nguyen and Meyer, a literature review revealed that the minor complication rate was 18.2% for open biopsy and 9.6% for VATS biopsy, while mortality rates were 4.3% for open biopsy and 2.1% for VATS biopsy (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In our study, both complication and mortality rates were lower than these figures, with the VATS technique being utilized in our clinic. Due to severe pleural adhesions, mini-thoracotomy was performed in 8 cases (3.2%), with partial pneumolysis carried out to create a resectable area. No mortality was observed in the mini-thoracotomy group.\u003c/p\u003e \u003cp\u003eIn the study conducted by Otsuka et al., in 2022, 129 cases were analyzed and 26.4% of the cases could not be classified based on their pathological diagnoses and were categorized as unclassifiable idiopathic interstitial pneumonia As the number of biopsies performed on the same case increases, the rate of achieving a surgical diagnosis also rises; however, this also creates a predisposition for complications. While this study reported a rate of 9% for biopsies performed from three different lobes, in our study, this was done in 3% of cases. In the study by Otsuka et al., the complication rate was found to be 10.1%, while no mortality was observed. Resections performed from the apical portion of segment S1 in the upper lobe showed an increased incidence of postoperative pneumothorax compared to other upper lobe segments, while no increased risk was observed in wedge resections performed in the lower lobes (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In our clinic, the apical region is generally not used as a procedure.\u003c/p\u003e \u003cp\u003eIn a meta-analysis conducted by Han et al., 2,148 cases from 23 studies were evaluated, and the median rate of diagnosis through surgical biopsy was reported as 95%. The diagnostic rate ranged from 42% to 100%, with only one study reporting a rate below 70%. When comparing six studies that applied both VATS and open surgery, no significant difference was observed in the determination of the pathological diagnosis. In the pathological specimen evaluation, idiopathic pulmonary fibrosis was the most common diagnosis at 33.5%, followed by NSIP at 11.9% and HP at 9.6% (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). In our study, the rate of definitive diagnosis was 92.1%, and the most common diagnosis in the pathological specimen evaluation was hypersensitivity pneumonitis at 43.9%, followed by idiopathic pulmonary fibrosis at 17.8%.\u003c/p\u003e \u003cp\u003eIn the study conducted by Fibla et al., 311 cases underwent surgical biopsy, and 74.6% achieved a specific, definitive diagnosis. The most common diagnoses were idiopathic pulmonary fibrosis at 39% and cryptogenic organizing pneumonia at 10%. In the cases, 77% started a new treatment, 40.7% had a change in the treatment strategy, and 6.8% discontinued the previous treatment. In our study, 77.8% of cases started medical treatment, while 68.8% of cases in the IAH subgroups began specific treatment. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). It is evident that these studies provided therapeutic benefits for the disease through definitive diagnosis.\u003c/p\u003e \u003cp\u003eAfter clinical and radiological evaluation, the diagnostic rates through bronchoscopy and transbronchial cryobiopsy are high, and typical UIP cases in smokers can receive a diagnosis. In the pathology review of our study, hypersensitivity pneumonia was the most commonly observed condition, along with specific and rare subdiagnoses, indicating that the cases referred for surgery were optimally selected. Being a specialized center in pulmonology and thoracic surgery, and a tertiary hospital, with extended procedures being performed and a high annual patient intervention rate, this is an experienced institution. It is crucial to plan the diagnosis and treatment of specialized groups, such as interstitial lung diseases, through a multidisciplinary approach.\u003c/p\u003e"},{"header":"Limitation","content":"\u003cp\u003eTransbronchial cryobiopsy has been actively used in our clinic in recent years. However, during the course of the study, it was not used equally throughout the periods due to technical issues. Although all patients who underwent surgical lung biopsy were included in the study, the total number of patients evaluated for interstitial lung disease during this process is unknown.\u003c/p\u003e \u003cp\u003eThis study included a heterogeneous group of interstitial lung disease subtypes diagnosed through surgical biopsy. Although our center is a national reference unit with high procedural volume, the diversity of diagnoses limited standardized follow-up of pulmonary function across subgroups. Additionally, a prospective protocol for systematic pre- and post-biopsy pulmonary function testing was not implemented during the study period. Future studies focusing on specific diagnostic subgroups with structured functional follow-up are needed to better understand the impact of surgical lung biopsy on respiratory function.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSurgical lung biopsy is recommended for unclassified ILD, clinical high-resolution CT or transbronchial lung biopsy groups that cannot be classified. It can be said that surgical biopsy with VATS can be performed safely and provides a significant therapeutic benefit in this patient group. It remains the gold standard in the diagnosis of ILD due to its high rate of definitive diagnosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of interest:\u003c/h2\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003ch2\u003eEthics Committee Approval\u003c/h2\u003e\n\u003cp\u003eThe study was approved by the ethics/scientific committee of Tekirdag Dr. Ismail Fehmi Cumalıoglu City Hospital and was conducted by the principles of the Declaration of Helsinki by the number 91/2024. A written informed consent was obtained from each patient\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication of identifying images or other personal or clinical details of the participants has been obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Sharing Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eThis research did not receive any specific grant from any funding agencies.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eAuthor Contributions: Conceptualization: M\u0026Uuml;, BDData curation: M\u0026Uuml;, DK, REFormal analysis: M\u0026Uuml;Funding acquisition: VEInvestigation: M\u0026Uuml;, BD, E\u0026Ccedil;Methodology: M\u0026Uuml;, E\u0026Ccedil;, MMProject administration: M\u0026Uuml;Resources: M\u0026Uuml;, CBSSoftware: M\u0026Uuml;Supervision: MM, E\u0026Ccedil;Validation: M\u0026Uuml;Writing-original draft: M\u0026Uuml;, E\u0026Ccedil;Writing-review\u0026amp;editing: M\u0026Uuml;\u003c/p\u003e\n\u003ch2\u003eAcknowledgment:\u003c/h2\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHunninghake GW, Zimmerman MB, Schwartz DA, King TE, Lynch J, Hegele R. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2001;164:193\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhalil M, Cowen M, Chaudhry M, Loubani M. Single versus multiple lung biopsies for suspected interstitial lung disease. Asian Cardiovasc Thorac Annals 2016, 24(8) 788\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSedrakyan A, van der Meulen J, Lewsey J, Treasure T. Video-assisted thoracic surgery of treatment of pneumothorax and lung resections: systematic review of randomized clinical trials. BMJ. 2004;329:1008\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang D, Liu Y. Surgical lung biopsies in 418 patients with suspected interstitial lung disease in China. Intern Med. 2010;49:1097\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark JH, Kim DK, Kim DS, Koh Y, Lee S, Kim WS, et al. Mortality and risk factors for surgical lung biopsy in patient with idiopathic interstitial pneumonia. Eur J Cardiothorac Surg. 2007;31:1115\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRicheldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet. 2017;389:1941\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTuran D, Uğur Chousein EG, Ko\u0026ccedil; AS, \u0026Ccedil;\u0026ouml;rt\u0026uuml;k M, Yıldırım Z, Demirkol B, et al. Transbronchial cryobiopsy for diagnosing parenchymal lung diseases: real-life experience from a tertiary referral center. Sarcoidosis Vasc Diffuse Lung Dis. 2021;38(1):e2021004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLieberman S, Gleason JB, İlyas MIM, Martinez F, Mehta J, Savage EB. Assessing the safety and clinical impact of thoracoscopic lung biopsy in patients with interstitial lung disease. J Clin Diagn Res. 2017 Mar,Vol-11(3):57\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDurheim MT, Kim S, Gulack BC, Burfeind WR, Gaissert H, Kosinski AS, et al. Mortality and respiratory failure after thoracoscopic lung biopsy for interstitial lung disease. Ann Thorac Surg. 2017;104(2):465\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNguyen W, Meyer KC. Surgical lung biopsy for the diagnosis of interstitial lung disease: a review of the literature and recommendations for optimizing safety and efficacy. Sarcoidosis Vasc Diffuse Lung Dis. 2013;30:3\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOtsuka H, Sano A, Azuma Y, Sakai T, Koezuka S, Sugino K, et al. Surgical lung biopsy for interstitial lung diseases: a single center study of 129 patients. J Thorac Dis. 2022;14(6):1972\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHan Q, Luo Q, Xie JX, Wu L, Liao L, Zhang X, et al. Diagnostic yield and postoperative mortality associated with surgical lung biopsy for evaluation of interstitial lung diseases: A systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2015;149:1394\u0026ndash;401.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFibla JJ, Brunelli A, Cassivi SD, Deschamps C. Aggregate risk score for predicting mortality after surgical biopsy for interstitial lung disease. Interact Cardiovasc Thorac Surg. 2012;15(2):276\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e\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":"Interstitial lung disease, surgical biopsy, VATS","lastPublishedDoi":"10.21203/rs.3.rs-8961011/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8961011/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eInterstitial lung disease encompasses a wide range of conditions, with treatments tailored according to subgroup diagnoses. Surgical biopsy is recommended when a diagnosis cannot be established through clinical and radiological evaluations, or when the clinical course is uncertain.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eCases of surgical biopsy performed for interstitial lung disease from 2018 to 2023 were retrospectively analyzed. Postoperative complications, mortality rates, definitive diagnoses, and treatments were evaluated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTotally 253 patients were included in the study, comprising 150 males (59.3%) and 103 females (40.7%). The mean age was 58.4\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5 years. Minor complications were observed in 14 cases (5.5%), while major complications occurred in 7 (2.8%). Mortality was reported in two cases (0.8%) within the series. All patients who received a definitive diagnosis were initiated on disease-specific treatments. Medical treatment was initiated for 197 cases (77.8%). Specific treatment was started for 174 cases (68.8%) following the determination of an interstitial subgroup diagnosis.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSurgical biopsy performed via VATS is a safe procedure that provides significant therapeutic benefits by enabling a definitive diagnosis for patients with interstitial lung disease.\u003c/p\u003e","manuscriptTitle":"The Role of Surgical Lung Biopsy in Diagnosis and Treatment Guidance for Interstitial Lung Diseases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-13 05:28:16","doi":"10.21203/rs.3.rs-8961011/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-12T11:55:14+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-11T14:43:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"316911845102759282364153197324690671176","date":"2026-05-11T13:55:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-07T12:03:03+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T17:58:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"150668674516825648143309961120944239020","date":"2026-05-06T11:40:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"126154522358081369165094176513057176602","date":"2026-05-04T10:01:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-04T09:20:17+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-05-04T06:14:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-04T10:05:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-28T21:23:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2026-02-28T21:19:44+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":"7cffad7e-bd5f-41ee-b15f-3f6ea61122f7","owner":[],"postedDate":"May 13th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-12T11:55:14+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-11T14:43:07+00:00","index":34,"fulltext":""},{"type":"reviewerAgreed","content":"316911845102759282364153197324690671176","date":"2026-05-11T13:55:45+00:00","index":33,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-07T12:03:03+00:00","index":30,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T17:58:47+00:00","index":29,"fulltext":""},{"type":"reviewerAgreed","content":"150668674516825648143309961120944239020","date":"2026-05-06T11:40:01+00:00","index":28,"fulltext":""},{"type":"reviewerAgreed","content":"126154522358081369165094176513057176602","date":"2026-05-04T10:01:06+00:00","index":26,"fulltext":""},{"type":"reviewersInvited","content":"6","date":"2026-05-04T09:20:17+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-05-04T06:14:01+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T05:28:17+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-13 05:28:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8961011","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8961011","identity":"rs-8961011","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}