Prevalence and risk factors of depression and anxiety for inpatients with lung cancer in China: A hospital-based cross-sectional study

Lung cancer was often accompanied by depression and anxiety. Nowadays, most investigations for depression and anxiety were concentrated in western medical hospitals, while few related studies have been carried out in the tradition Chinese medicine (TCM) ward. It was necessary to understand the prevalence and risk factors of depression and anxiety in the inpatients with lung cancer in TCM hospital. This study adopted cross-sectional research method, which enrolled a total of 222 inpatients with lung cancer in TCM hospital. PHQ-9 and GAD-7 scales were used to assess depression and anxiety for the inpatients, respectively. Demographic and clinical data were also collected. Statistical methods of the univariate analysis and the multivariate logistic regression model were used.


Introduction
Lung cancer was the most common cancer and the leading cause of cancer death in China and worldwide [1] . In recent years, the incidence of lung cancer had increased substantially in China and was likely to continue to rise in the next few decades [2] . Most patients with lung cancer usually confronted a limited life span and had to receive surgery, chemical radiotherapy, targeted therapy, and other treatments. Bene ting from the development of treatment methods, more and more patients with lung cancer could receive more treatments to survive longer. However, these treatments and the disease of lung cancer itself often caused many uncomfortable symptoms, impaired physical function, nancial burden, social tension and psychological disorders. Besides the e cacy of cancer treatment, these issues should also arouse our widespread concern. In particular, the low cure rate, limited overall survival, and continuous therapies leaded the patients to experience considerable psychological disorder, which should arouse widespread attention from doctors and nurses engaged in clinical work of lung cancer [3] .
Nowadays, the psychological disorder of patients with cancer had been determined by National Comprehensive Cancer Network (NCCN) guidelines as the sixth vital characteristic besides body temperature, pulse, breathing, blood pressure, and pain [4] . Depression and anxiety as the most common psychological disorders also most troubled the patients with lung cancer [5] . Extensive studies had shown that the incidence of depressive and anxious in the patients with lung cancer were 38.9-57.1% and 20.9-43.5% respectively [6][7][8] . In addition, the research revealed that cancer patients with depression and anxiety had not only a worse quality of life, but also longer hospital stay and higher costs [9][10] . And psychological disorder of depression and anxiety had been regarded as a predictor of shorter survival in patients with lung cancer [11] . Therefore, it was very meaningful to investigate the symptoms of depression and anxiety in patients with lung cancer and explored the in uencing factors of them in order to better understand and respond.
Nowadays, we had obtained the data related to depression and anxiety in patients with lung cancer, which were mainly from western medical hospitals [6][7] . Only a few investigations on depression and anxiety on patients with lung cancer were carried out in TCM hospitals, but only in outpatients [8] . It was widely known that Chinese medicine therapy was different from the western medicine, and the characteristics of outpatients and inpatients were also very different. This study intended to use internationally recognized scales to assess the prevalence of depression and anxiety in the inpatients with lung cancer of TCM hospital, and to determine the related risk factors of depression and anxiety.

Participants
The cross-sectional study recruited patients with lung cancer who were hospitalized in the Oncology Department of Guang'anmen Hospital, a Grade 3A TCM hospital in Beijing, between January 1 and December 31, 2019. The diagnosis and Tumor Node Metastasis (TNM) staging of lung cancer referred to "Chinese guidelines for diagnosis and treatment of primary lung cancer 2018 (English version)" [12] .

Procedures
The proposal was approved by the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences (reference number:2016-048-KY-02). Potential participants were approached and invited to this study on the rst day when they were admitted to the hospital ward. This was a convenience sample. The study was conducted in the oncology ward of Guang'anmen Hospital. After the inclusion criteria of patients were determined, the method and purpose of the research were explained to them. After the patients provided written informed consent, their information was collected. The study was conducted in compliance with the Declaration of Helsinki.

Measurements
All evaluation data would be collected on the rst day of patients' hospitalization. (1) General information including name, age, gender, and medical insurance. (2)Clinical information including: Disease course(days), treatment method(surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy), BMI, NRS score, KPS score, pathological classi cation, TNM staging, tobacco smoking, and other chronic comorbid conditions information. (3)Clinical symptoms including: poor appetite, cough, constipation, diarrhea and insomnia. (4)Observation indexes were PHQ-9(9-Item Patient Health Questionnaire) [13] and GAD-7(7-Item Generalized Anxiety Disorder ) [14] scales score, which had been validated to Chinese for evaluating the depression and anxiety respectively [15] . General information and partial clinical information were gathered from the medical records available. Another partial clinical information, clinical symptoms and observation indexes of two scales score were obtained from the patients directly.
Anxiety GAD-7 [17] was a questionnaire designed to assess anxiety symptoms. Patients were invited to answer 7 questions assessing past two-weeks period. Questions: (1) Feeling nervous, anxious or on edge;(2) Not being able to stop or control worrying; (3) Worrying too much about different things; (4) Trouble relaxing; (5) Being so restless that was hard to sit still;(6) Becoming easily annoyed or irritable; (7) Feeling afraid as if something awful might happen. Four alternatives are offered: (A)Not at all;(B) Several days;(C) More than half the days;(D) Nearly every day. Scores could range from 0 to 21. Total score 0-4 points indicated no anxiety, 5-9 indicated mild anxiety,10-13 indicated moderate anxiety,14-18 indicated moderate and severe anxiety, and 19-21 indicated severe anxiety.

Chronic comorbid conditions and Physical symptom burden
To analyze the chronic comorbid conditions and physical symptoms associated with depression and anxiety, four common chronic medical conditions were added: Hypertension, Diabetes Mellitus, Coronary Heart Disease, Hyperlipidemia. And ve common physical symptoms were added: insomnia, cough, constipation, diarrhea and poor appetite, which assessed by Guidelines for clinical research of Traditional Chinese Drug Research [18] .

Statistical analyses
The SPSS 24.0 software was used for statistical analysis of all data, using a two-sided difference test. P ≤ 0.05 is considered statistically signi cant. Descriptive statistics for both continuous (frequencies, mean, standard deviation) and categorical variables (frequencies, percentages) were calculated. Comparisons between depression/anxiety and non-depression/non-anxiety groups were performed in a one-way analysis of variance. To identify signi cant factors associated with depression and anxiety inpatients with lung cancer, a multivariate logistic regression model was used after univariate analysis.

Characteristics of all participants
A total of 251 inpatients with lung cancer met the inclusion criteria. After excluding 15 participants not interested in the study, 10 patients with uncertain cancer diagnosis and 4 patients who did not complete the questionnaire, 222 patients completed the study (Figure 1). According to the rough estimation method of sample size, the sample size was 5-10 times the number of variables [19] [20] . The number of cases enrolled in this study throughout 2019 should meet the requirements. The general information clinical information and other symptoms data collected from 222 inpatients were presented in Table 1.   The signi cant risk factors of depression and anxiety were shown in Figure 2. Patients with insomnia were 3.274 times more likely to suffer from depression than those without insomnia and 2.201 times more likely to suffer from anxiety than those without insomnia. Female patients were1.298 times more likely to be depressed than men. Patients with constipation were1.458 times more likely to be depressive than non-constipated patients.

Discussion
The study was aimed to explore the prevalence of depression and anxiety in the inpatients with lung cancer in TCM hospital, and further to explore the risk factors of depression and anxiety. The patients with lung cancer hospitalized for the rst time in the oncology department of Guang'anmen hospital throughout 2019 were recruited. And the characteristics of the inpatients related to depression and anxiety were investigated. It was found that the prevalence of depression accounted for 58.1% and moderate or even more serious depression accounted for 25.7%. The prevalence of anxiety accounted for 34.2% and moderate or even more serious anxiety accounted for 8.6%.
For depression, regarding the prevalence of depression in the patients with lung cancer in China, our nding was higher than the researches of Xinmiao Wei(53.71%,in Guangxi Province) [21] , Guixiang Liu(43.3%,in Jiangsu Province) [22] ,and Hao Sun(48%,in Shanghai City) [23] et al in western medical hospitals, and even than slightly higher than the X Yan' research(57.1%) [8] on outpatients in Guang'anmen hospital. This might be related to the characteristics of patients who seek hospitalization treatment in TCM hospital. In China, most cancer patients were usually diagnosed in western medical hospitals and treated with all kinds of modern medical therapies. TCM was not usually considered until patients could not tolerate modern medical treatment or modern medical treatment failed to work. Patients in TCM hospitals usually had a longer course of disease and worse condition than those in western hospitals, which would lead to more depression in TCM hospital. This was basically consistent with Seul Ki Park' research results [24] , which suggested that patients would have a clearer understanding to their condition with the extension of the course of disease. When the disease progressed but not be signi cantly controlled or adverse reactions due to treatment appeared, the patients' depression would increase. Moreover, inpatients often came from outpatients whose diseases needed further treatment. Considering that data was collected on the rst day of patients' hospitalization, in this study the prevalence of depression in the inpatients was only 1% higher than that in the outpatients [8] .
The prevalence of anxiety in the patients with lung cancer from western medical hospitals was 50.71%~89.4% [25][26][27] .Comparing with the previous investigations, the prevalence of anxiety was reported in our study was lower. This might be related to the fact that patients treated in TCM hospitals generally were usually diagnosed or treated in western medical hospitals in the past. Research showed that anxiety was the main psychological disorder in the early stage of lung cancer. As time went on, anxiety would gradually decrease, which re ected the adaptation process to life-threatening [28] . In addition, some studies also suggested that patients' anxiety was obvious in the early and middle stages of cancer treatment, but the anxiety in the later stage generally could not increase or even decrease [29] . The prevalence of anxiety of the inpatients with lung cancer was lower than outpatients [8] in TCM hospital (34.2% vs 43.5%), which might be related to the fact that the patients who had been determined to be able to hospitalize could obtain certain psychological comfort and reduce anxiety [30] .
In the investigation, 53.6% of inpatients suffered from insomnia. The study result showed that both anxiety and depression were obviously associated with the symptoms of insomnia. Previous studies had also shown that patients with long-term insomnia would feel helpless and irritable and were more prone to feel depressed and anxious [31] . And longitudinal studies had suggested that cancer patients with persistent insomnia had a higher risk of depression and anxiety [32][33][34][35][36] . These results indicated that insomnia was a key risk factor for the depression and anxiety.
In addition, this study also found that both gender and constipation were the risk factors for depression.
In the study, the gender of female was more likely to have depression, which was 1.458 times that of male. This result had also been explained in many other studies [37] . However, there were few reports on the relationship between depression and constipation in patients with lung cancer. In clinic, inpatients often suffered from constipation. It might be related to the decrease of activity after hospitalization or related to the use of opioid painkillers because of cancer pain [38] . This suggested that we should pay more attention to the psychological status of patients with constipation. In clinic, once the inpatients had insomnia or constipation, doctors should actively improve them and strengthen psychological counseling.
The advantage of this study was to speci cally investigate the prevalence of depression and anxiety in the patients with lung cancer hospitalized in TCM hospital and explore the related risk factors.

Study Limitations
Due to the cross-sectional design of the analysis, this study could not be determined that the depression or anxiety and related symptoms appeared before or after diagnosis of lung cancer and changed throughout the course of the disease. Consequently, related longitudinal studies were necessary to carry out further. In addition, due to insu cient funds resulting in the limitation of sample size, the correlation analysis was not further carried out between the severity of depression/anxiety and the severity of symptoms. In the future, the sample size should be expanded for further analysis. Thirdly, due to limited research funds and time, only ve common clinical symptoms of inpatients were selected in this study, which was a de ciency. Finally, this study was only a single-center study, which might lead to certain selection bias.

Clinical Implications
This study showed that the inpatients with lung cancer in TCM hospital had a high prevalence of depression and anxiety. Meanwhile, the possible reasons for the difference of the prevalence of depression and anxiety among the inpatients in TCM hospital, the patients in western medical hospital and the outpatients in TCM hospital were analyzed. This study also showed gender, insomnia and constipation were risk factors for depression, and insomnia was risk factor for anxiety. Conclusions indicated that the psychological disorders of inpatients with lung cancer in TCM hospital should be paid more attention to. And the common clinical symptoms such as insomnia and constipation should also be concerned as early as possible.

Conclusion
This study demonstrated that depression and anxiety were very common in the patients with lung cancer hospitalized in TCM hospital. The variables of gender, insomnia and constipation was the independently risk factors for the depression, and insomnia was for anxiety. Therefore, medical workers should pay close attention to the emotional changes of these high-risk patients. Consent for publication Written informed consent for publication was obtained from all participants.  Multivariate analysis of factors in depression and anxiety