Research on Regional Differences in Clinical Characteristics and Basic Syndrome Patterns Among 2,340 Lung Cancer Patients Across China

FENG Zhenzhen¹², LIU Wenrui¹², LI Jiansheng¹²*, GUAN Xutao³, QUAN Jianfeng⁴, GAO Hong⁵, TIAN Jianhui⁶, RONG Zhen⁷, HOU Wei⁸, ZHOU Xun⁹

¹National Regional Traditional Chinese Medicine (Lung Disease) Diagnosis and Treatment Center, First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China
²Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province & Ministry of Education/Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou 450046, China
³Department of Hematology and Oncology, First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China
⁴Department of Oncology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, China
⁵Department of Oncology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110000, China
⁶Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai 200071, China
⁷Department of Oncology, First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning 530023, China
⁸Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
⁹Department of Respiratory Medicine, Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550003, China

Corresponding author: LI Jiansheng, Professor/Chief Physician/Doctoral Supervisor; E-mail: li_js8@163.com

Abstract

Background: Traditional Chinese Medicine (TCM) theory posits a close relationship between syndrome patterns and geographical regions. However, clinical research investigating regional variations in clinical characteristics and TCM syndrome distributions among lung cancer patients remains insufficient.

Objective: To analyze regional differences in clinical characteristics and TCM syndrome distributions among lung cancer patients across various regions in China, providing evidence to support clinical syndrome differentiation.

Methods: A cross-sectional survey was conducted from June 2020 to June 2024. Questionnaires were distributed to outpatient and inpatient lung cancer patients at 11 hospitals: Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, Henan Cancer Hospital, First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, and Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine. Patients were grouped into seven geographical regions: Northeast, North China, East China, South China, Central China, Northwest, and Southwest. General characteristics including age, gender, ethnicity, tumor node metastasis (TNM) staging, pathological type, treatment methods, smoking history, chronic respiratory disease comorbidities, family history of tumors, living environment, and TCM syndromes (lung qi deficiency, blood stasis, lung yin deficiency, etc.) were compared across regions.

Results: A total of 2,400 questionnaires were distributed, with 2,340 valid responses collected. Significant regional differences were observed in patient age, gender, ethnicity, TNM stage, pathological type, treatment modality, smoking history, chronic respiratory disease comorbidities, family history of tumors, living environment, and self-assessment scores (pain, quality of life, functional status, physical condition, anxiety, depression) (P<0.05). The overall frequency of basic lung cancer syndromes across all regions, from highest to lowest, was: lung qi deficiency, blood stasis, lung yin deficiency, spleen qi deficiency, phlegm-dampness, and phlegm-heat syndrome, with significant regional variations (P<0.05). Specifically, the predominant syndromes were lung qi deficiency (37.11%), lung yin deficiency (33.51%), and phlegm-dampness (20.10%) in the Northeast; lung qi deficiency (85.19%), blood stasis (72.84%), and lung yin deficiency (44.44%) in North China; lung qi deficiency (69.15%), lung yin deficiency (44.47%), spleen qi deficiency (19.15%), and blood stasis (19.15%) in East China; lung qi deficiency (58.50%), lung yin deficiency (37.00%), and phlegm-dampness (21.00%) in South China; lung qi deficiency (51.51%), blood stasis (35.92%), and spleen qi deficiency (35.92%) in Central China; lung qi deficiency (74.00%), spleen qi deficiency (58.00%), and blood stasis (51.00%) in Northwest China; and blood stasis (31.34%), lung qi deficiency (28.26%), and lung yin deficiency (18.41%) in Southwest China.

Conclusion: Regional variations exist in the clinical characteristics and TCM syndrome distributions among lung cancer patients in China. TCM syndrome differentiation and treatment should therefore consider both geographical and individual factors to enhance clinical efficacy.

Keywords: lung cancer; Traditional Chinese Medicine; syndrome; regional differences; clinical research

Introduction

According to the latest global cancer statistics and data from China's National Cancer Center, lung cancer ranks first in both mortality and incidence among malignant tumors in China and worldwide [1-2]. In 2022, approximately 1.06 million new lung cancer cases were reported in China, accounting for about 22% of all malignant tumors, with deaths reaching 733,300 cases, representing approximately 28.5% of all cancer-related deaths [2]. Traditional Chinese Medicine has demonstrated unique advantages in treating lung cancer at all stages [3]. Syndrome differentiation and holistic concept represent the distinctive features of TCM diagnosis and treatment, emphasizing comprehensive consideration of patient pathogenesis and environmental factors to achieve individualized care [4]. TCM theory suggests a close relationship between syndrome patterns and geographical regions [5]; however, clinical research investigating regional differences in clinical characteristics and syndrome distributions among lung cancer patients remains scarce. This study analyzed data from 2,340 lung cancer patients across seven regions of China (Northeast, North China, East China, South China, Central China, Northwest, and Southwest) to explore differences in clinical characteristics and syndrome distributions, aiming to provide reference for clinical diagnosis and treatment of lung cancer.

Methods

Study Design and Participants

This cross-sectional study employed cluster sampling to recruit 2,340 lung cancer patients from outpatient and inpatient departments at 11 hospitals between June 2020 and June 2024. The participating hospitals were: Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, Henan Cancer Hospital, First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, and Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine. According to China's administrative regional divisions, cases were categorized into seven regions: Northeast (Liaoning), North China (Beijing), East China (Shandong, Shanghai), South China (Guangxi), Central China (Henan), Northwest (Shaanxi), and Southwest (Chengdu and Yunnan). The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine (Approval No.: 2020HL-083).

Inclusion criteria: (1) Patients meeting lung cancer diagnostic criteria; (2) Age ≥ 18 years; (3) Self-reported ability to communicate orally in Chinese; (4) Voluntary participation with signed informed consent.

Exclusion criteria: (1) Patients unsuitable for research participation, such as pregnant/lactating women, critically ill/terminal patients, or those with severe depression/anxiety; (2) Patients with cognitive or other impairments (e.g., vision, hearing, speech, mobility) affecting self-report completion.

Diagnostic Criteria

Western medicine diagnostic criteria: Referenced the "Chinese Medical Association Lung Cancer Clinical Diagnosis and Treatment Guidelines (2019 Edition)" [6], with diagnosis established through sputum cytology, lymph node or nodule biopsy, and other methods.

TCM syndrome diagnostic criteria: Referenced "Traditional Chinese Medicine Clinical Terminology: Syndrome Part: GB/T16751.2-1997" [7], "Tumor TCM Diagnosis and Treatment Guidelines: ZYYXH/T136~156-2008" [8], "Routine Diagnosis and Treatment of TCM Internal Medicine Diseases: National Standard Application" [9], and "Evidence-based Clinical Practice Guidelines in Chinese Medicine - Internal Medicine Volume" [10]. For example, lung qi deficiency syndrome was diagnosed based on low and weak coughing, shortness of breath, wheezing, thin clear white sputum, poor appetite, chest tightness, fatigue, spontaneous sweating, aversion to cold, pale tender tongue with white coating, and weak pulse.

Data Collection

General data collection: Included age, gender, ethnicity, TNM staging, pathological type, treatment methods, smoking history (defined as current smokers or those who had quit), family history of tumors, comorbid chronic respiratory diseases (including chronic bronchitis, COPD, asthma, idiopathic pulmonary fibrosis, tuberculosis, pneumoconiosis, chronic pharyngitis, allergic rhinitis, etc.), and living environment.

TCM syndrome collection: Included lung qi deficiency syndrome, blood stasis syndrome, lung yin deficiency syndrome, spleen qi deficiency syndrome, phlegm-dampness syndrome, phlegm-heat syndrome, qi stagnation syndrome, kidney qi deficiency syndrome, kidney yin deficiency syndrome, stomach qi deficiency syndrome, blood deficiency syndrome, lung heat syndrome, and kidney yang deficiency syndrome.

Patient self-assessment: (1) Pain: assessed using the Visual Analogue Scale (VAS) [11], scored 0-10 (0 = no pain, 10 = worst pain); (2) Physical condition: assessed using the Eastern Cooperative Oncology Group (ECOG) Performance Status scale [12], scored 0-5 (0 = normal activity, 5 = death); (3) Functional status: assessed using the Karnofsky Performance Status (KPS) scale [13], scored 0-100 (higher scores indicate better functional status); (4) Quality of life: assessed using the Quality of Life Questionnaire Core 30 (QLQ-C30) [14], including physical, role, social, and emotional functioning, scored 0-100 (higher scores indicate better quality of life); (5) Anxiety: assessed using the Self-Rating Anxiety Scale (SAS) [15], comprising 20 items scored 1-4 based on severity, with higher total scores indicating greater anxiety; (6) Depression: assessed using the Self-Rating Depression Scale (SDS) [16], comprising 20 items scored 1-4 based on severity, with higher total scores indicating greater depression.

Quality control: A quality control team was established to develop unified clinical research protocols. Investigators at each center received on-site or online training before data collection, with inter-rater reliability assessed using Kappa tests. The quality control team conducted regular sampling and verification of study cases.

Statistical Analysis

Data were analyzed using IBM SPSS 26.0 software. Categorical data were expressed as frequencies and percentages, with inter-group comparisons using chi-square tests or Fisher's exact test. Continuous data were non-normally distributed and thus described using median (P25, P75), with inter-group comparisons using Kruskal-Wallis tests. Categorical missing data were imputed using mode, and quantitative missing data using median. P<0.05 was considered statistically significant.

Results

Comparison of General Characteristics Across Regions

A total of 2,340 lung cancer patients were included: Northeast (Liaoning) 194 cases (8.29%), North China (Beijing) 81 cases (3.46%), East China (Shandong, Shanghai) 470 cases (20.09%), South China (Guangxi) 200 cases (8.55%), Central China (Henan) 994 cases (42.48%), Northwest (Shaanxi) 200 cases (8.55%), and Southwest (Chengdu and Yunnan) 201 cases (8.59%). Significant regional differences were observed in age, gender, ethnicity, TNM stage, pathological type, treatment modality, smoking history, chronic respiratory disease comorbidities, family history of tumors, and living environment (P<0.05). The median age across all seven regions was >60 years, with male and Han ethnicity predominating. North China had the highest proportion of male patients [59 cases (72.84%)], while Northeast had the highest proportion of female patients [95 cases (48.97%)]. For TNM staging, Stage IV patients accounted for the highest proportion in all regions (27.36%-74.07%). For pathological types, adenocarcinoma was most common across all regions (32.84%-73.00%), while squamous cell carcinoma was relatively more prevalent in North China and Northwest (25.92% and 26.50%, respectively), and small cell lung cancer was relatively more common in Northeast, Central China, and Northwest (15.98%, 15.09%, and 14.50%, respectively). Regarding treatment modalities, Northeast commonly used chemotherapy (42.78%), surgery (35.05%), and targeted therapy (26.29%); North China primarily used chemotherapy (93.83%); East China frequently used chemotherapy (57.87%), surgery (47.87%), and targeted therapy (26.60%); Central China often used chemotherapy (72.43%), targeted therapy (41.35%), and surgery (17.30%); Northwest commonly used chemotherapy (71.50%), targeted therapy (38.00%), and radiotherapy (21.00%); and Southwest frequently used chemotherapy (39.30%), immunotherapy (22.89%), and surgery (19.90%). Smoking history was >50% in Northwest, Southwest, East China, and North China. Comorbid chronic respiratory diseases were more prevalent in East China and Southwest (25.74% and 22.89%, respectively), with chronic bronchitis being the most common across all regions. East China had the highest proportion of patients with a family history of tumors (15.96%). Except for Central China, urban living environments predominated over rural in all regions [TABLE:1].

Comparison of Multi-Dimensional Self-Assessment Scores Across Regions

Significant regional differences were observed in VAS, KPS, ECOG, QLQ-C30, SAS, and SDS scores (P<0.05). South China and Central China patients had relatively higher VAS scores [3 (1.25, 4) and 2 (0, 4), respectively]. Northeast and Central China patients had lower KPS scores [80 (60, 90) and 80 (70, 90), respectively]. Northeast and Central China patients had higher ECOG scores [2 (1, 3) and 2 (1, 2), respectively]. North China patients had the highest QLQ scores [71.43 (57.14, 71.43)], while South China and Central China had relatively lower scores. South China patients had the highest SAS [43.00 (37.00, 48.75)] and SDS scores [50.00 (45.00, 52.00)], while North China had the lowest SAS [27.00 (26.00, 29.00)] and SDS scores [31.00 (30.00, 34.00)] [TABLE:2].

Comparison of Basic Syndrome Distribution Across Regions

The most common basic syndromes across the seven regions were, in descending order: lung qi deficiency, blood stasis, lung yin deficiency, spleen qi deficiency, phlegm-dampness, phlegm-heat, qi stagnation, kidney qi deficiency, kidney yin deficiency, stomach qi deficiency, blood deficiency, lung heat, and kidney yang deficiency. Significant regional differences were observed in the distribution of lung qi deficiency, blood stasis, lung yin deficiency, spleen qi deficiency, phlegm-dampness, phlegm-heat, qi stagnation, kidney qi deficiency, kidney yin deficiency, and stomach qi deficiency syndromes (P<0.05). No significant regional differences were found in blood deficiency or kidney yang deficiency syndromes (P>0.05) [TABLE:3].

Specifically, the predominant syndromes were: lung qi deficiency (37.11%), lung yin deficiency (33.51%), and phlegm-dampness (20.10%) in Northeast; lung qi deficiency (85.19%), blood stasis (72.84%), and lung yin deficiency (44.44%) in North China; lung qi deficiency (69.15%), lung yin deficiency (44.47%), spleen qi deficiency (19.15%), and blood stasis (19.15%) in East China; lung qi deficiency (58.50%), lung yin deficiency (37.00%), and phlegm-dampness (21.00%) in South China; lung qi deficiency (51.51%), blood stasis (35.92%), and spleen qi deficiency (35.92%) in Central China; lung qi deficiency (74.00%), spleen qi deficiency (58.00%), and blood stasis (51.00%) in Northwest; and blood stasis (31.34%), lung qi deficiency (28.26%), and lung yin deficiency (18.41%) in Southwest.

Discussion

TCM theory holds that differences in climate and lifestyle across regions lead to distinct clinical characteristics and syndrome distribution patterns, as noted in Suwen·Yifa Fangyi Lun: "One disease treated differently, all cured... determined by geographical conditions" [17]. However, relevant clinical research remains limited. This study included 2,340 lung cancer patients from seven regions (Northeast, North China, East China, South China, Central China, Northwest, and Southwest) to explore regional differences in clinical characteristics and syndrome distributions, providing reference for region-adapted clinical management.

The results show that while regional differences exist in age, gender, pathological type, and treatment modality, common patterns emerge across regions: median age >60 years, male and Han ethnicity predominance, highest proportion of intermediate-advanced stage patients, and adenocarcinoma as the most common pathological type, consistent with previous research [2,18]. Regarding treatment selection, chemotherapy was most common across all regions, but surgery rates were higher in Northeast and East China where early-stage patients were relatively more numerous; North China, dominated by advanced-stage cases, primarily used chemotherapy; and targeted therapy rates were relatively higher in South China, Central China, and Northwest. These variations may relate to regional differences in early screening普及性 [19-20], driver gene mutation patterns in non-small cell lung cancer [21-22], and targeted drug accessibility [23-24].

Smoking history rates were high across all regions, consistent with previous findings [25], yet Northeast, South China, and Central China had more non-smoking patients, likely related to higher proportions of female patients. The proportion of non-smoking female lung cancer patients in China far exceeds that in other countries [26], making exploration of clinical characteristics in non-smoking patients crucial for early screening, particularly in regions with high non-smoking proportions [27-28].

Comorbid chronic respiratory disease rates ranged from 4.64% to 25.74% across regions, with chronic bronchitis being most common. Chronic pulmonary inflammation is a risk factor for lung cancer, promoting carcinogenesis through oxidative stress, immunosuppressive microenvironments, and abnormal signaling pathways [29], a view supported by this study. Researchers have already initiated TCM prevention and treatment studies based on the "inflammation-cancer" transformation mechanism [30-31]. Except for Central China, urban living environments predominated, consistent with National Cancer Center data showing slightly higher cancer rates in urban versus rural areas [32].

Multi-dimensional self-assessment revealed regional differences in pain, functional status, physical condition, overall quality of life, anxiety, and depression. South China and Central China patients had relatively higher pain scores, poorer overall quality of life, and higher anxiety and depression scores, while North China patients showed better self-assessment across all domains. These differences may relate to regional economic levels and emphasis on quality of life, psychological status, and cancer symptom management.

Regarding basic syndrome distribution, lung qi deficiency was the most common deficiency syndrome across all seven regions, while blood stasis was the most common excess syndrome in North China, East China, Central China, Northwest, and Southwest, and phlegm-dampness predominated in Northeast and South China. The Northeast's cold climate (average winter temperature -20°C) [33] causes cold to constrict qi, resulting in more qi stagnation; the region's bold culture and preference for rich foods [34] easily generates phlegm-dampness. North China's cold, dry climate [35] causes blood stasis through cold coagulation and yin deficiency through dryness, leading to high rates of lung qi deficiency, blood stasis, and lung yin deficiency. East China's warm, humid climate, combined with rapid urbanization and severe air pollution [36], contributes to frequent respiratory diseases; this study found East China had the most patients with chronic respiratory diseases and high smoking rates, resulting in prevalent lung qi and yin deficiency. South China's warm, rainy climate [37] makes dampness a common pathogenic factor [38], leading to high phlegm-dampness rates. Central China, described in classical texts as "flat and damp...with mixed diets" [17], shows high rates of spleen qi deficiency and blood stasis. Northwest residents "eat much raw, cold food and dairy" [39], resulting in spleen and stomach qi deficiency; impaired spleen transformation leads to lung qi deficiency and blood stasis. Southwest's warm, humid climate produces more phlegm-heat, while dampness stagnates qi, causing qi stagnation.

In summary, this study explored clinical characteristics and basic syndrome distributions among 2,340 lung cancer patients across seven regions, revealing regional differences in age, gender, pathological type, quality of life, and syndrome patterns influenced by climate, diet, and cultural factors. These findings provide reference for region-adapted TCM management of lung cancer. However, limitations include: (1) Unequal sample sizes across regions, possibly related to population size or prevalence and potentially introducing selection bias; (2) Use of cluster sampling, which may involve sampling error. Future research will expand sample size, ensure regional balance, and employ combined cluster and stratified sampling to provide high-quality clinical evidence for individualized TCM lung cancer treatment.

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Funding: National Natural Science Foundation of China (82205313); Henan Provincial Science and Technology Research and Development Plan Joint Fund (Advantageous Discipline Cultivation Category) (232301420071); Henan Provincial Traditional Chinese Medicine Science Research Special Project (2022JDZX102)

Citation: FENG Z Z, LIU W R, LI J S, et al. Research on the differences in the clinical characteristics and basic pattern distribution of 2,340 lung cancer patients in different regions of China[J]. Chinese General Practice, 2025. DOI: 10.12114/j.issn.1007-9572.2025.0170. [Epub ahead of print]

Conflict of Interest: The authors declare no conflicts of interest.

Author Contributions: FENG Zhenzhen and LIU Wenrui contributed to manuscript writing, study implementation, quality control, and data collection and analysis; LI Jiansheng conceptualized the study, designed the protocol, supervised implementation, and revised the manuscript; LIU Wenrui, GUAN Xutao, QUAN Jianfeng, GAO Hong, TIAN Jianhui, RONG Zhen, HOU Wei, and ZHOU Xun contributed to clinical data collection.

Received: 2025-04-29
Revised: 2025-06-27
Accepted for publication: [Epub ahead of print]

Editor: LI Weixia