Correlation of Malnutrition，25-hydroxy Vitamin D and Interleukin-1β with Chronic Obstructive Pulmonary Disease in Elderly Inpatients
The specific pathogenesis of chronic obstructive pulmonary disease (COPD) is still not very clear so far, clinical interventions mainly focus on the control of pulmonary symptoms with drugs, however, the influence of extrapulmonary related factors of COPD has not caused enough attention.
To explore the correlation of malnutrition, 25-hydroxy vitamin D and interleukin-1β with COPD in elderly inpatients.
A total of 305 inpatients (≥60 years old) were recruited from Department of Geriatrics, the First People's Hospital of Yunnan Province from November 2020 to August 2021, and divided into COPD group (n=89) and non-COPD group (n=216) according to the incidence of COPD. General information and comprehensive geriatric assessment results were compared between the two groups; binary Logistic regression analysis was used to analyze the influencing factors of COPD in elderly inpatients, and Spearman rank correlation analysis was used to analyze the correlation of malnutrition, 25-hydroxy vitamin D and interleukin-1β with COPD.
There were significant differences in age, gender, current smoking rate, nutritional status, cognitive function, incidence of anxiety and depression, incidence of disability, sleeping status, frailty status, proportion of multiple drugs, kinds of drugs used, platelet count, C-reactive protein, total protein, albumin, thyroxine, 25-hydroxy vitamin D, estradiol, testosterone, prothrombin time, D-dimer, interleukin-6 and interleukin-1β between the two groups (P<0.05) . The results of binary Logistic regression analysis showed that, current smoking〔OR=2.351, 95%CI (1.053, 5.249) 〕, underlying malnutrition〔OR=2.429, 95%CI (1.118, 5.276) 〕, malnutrition〔OR=3.936, 95%CI (1.355, 11.439) 〕, sleeplessness〔OR=2.584, 95%CI (1.094, 6.102) 〕, C-reactive protein〔OR=0.988, 95%CI (0.978, 0.999) 〕, 25-hydroxy vitamin D〔OR=0.929, 95%CI (0.880, 0.981) 〕and interleukin-1β〔OR=1.025, 95%CI (1.003, 1.047) 〕were independent influencing factors of COPD in elderly inpatients (P<0.05) . The results of Spearman rank correlation analysis showed that, malnutrition (rs=0.280, P<0.001) and interleukin-1β (rs=0.145, P=0.011) were positively correlated with the incidence of COPD in elderly inpatients, while 25-hydroxy vitamin D was negatively correlated with the incidence of COPD (rs=-0.264, P<0.001) .
Malnutrition, 25-hydroxy vitamin D and interleukin-1β are independent influencing factors of COPD in elderly inpatients. Among them, malnutrition and interleukin-1β are positively correlated with the incidence of COPD, while 25-hydroxy vitamin D is negatively correlated with the incidence of COPD.
Effect of Integrated Chinese and Western Medicine Treatment on Immune Factors in a Rat Model with Phlegm-heat Syndrome in Acute Exacerbation-stable Stage of Chronic Obstructive Pulmonary Disease
Secretory immunoglobulin A (sIgA) deficiency and immune imbalance caused by T lymphocyte aggregation in lung tissue are associated with the development of chronic obstructive pulmonary disease (COPD) . Human gastrointestinal and respiratory tracts have a typical mucosal structure, which are connected with the common mucosal immune system.
To examine the responses of some immune factors to integrated Chinese and Western Medicine treatment in a rat model with phlegm-heat syndrome during the acute exacerbation to stable stage of COPD.
A study was implemented between September 2019 and December 2020. Sixty SPF Sprague-Dawley rats were selected, and divided into five groups using the RAND function in Excel: control, COPD, acute exacerbation of COPD (AECOPD) , Western Medicine, and integrated Chinese and Western Medicine. Except the control group, other groups were exposed to cigarette smoke and heat, and received intranasal administration of lipopolysaccharide to develop COPD in acute exacerbation to stable stage with phlegm-heat syndrome. The intervention in the acute exacerbation stage lasted for 8 days, during which Western Medicine group received intragastric administration of solution containing moxifloxacin hydrochloride tablets (0.027 g·kg-1·d-1) and salbutamol sulfate tablets (0.41 mg·kg-1·d-1) , integrated Chinese and Western Medicine group received intragastric administration of solution containing Tongsai granules (7.2 g·kg-1·d-1) , moxifloxacin hydrochloride tablets (0.027 g·kg-1·d-1) , and salbutamol sulfate tablets (0.41 mg·kg-1·d-1) , the other three groups received intragastric administration of isotonic (0.9%) sodium chloride 2 ml per day. Subsequently, the intervention in the stable period lasted for 14 days, during which western medicine group received intragastric administration of salbutamol sulfate tablets 0.41 mg·kg-1·d-1, and the integrated Chinese and Western Medicine group received intragastric administration of BufeiYishen formula 4.42 g·kg-1·d-1 and salbutamol sulfate tablets 0.41 mg·kg-1·d-1. The other three groups received intragastric administration of isotonic (0.9%) sodium chloride 2 ml per day. The forced vital capacity (FVC) , forced expiratory volume during the first 300 milliseconds (FEV0.3) , FEV0.3/FVC ratio, and sIgA, as well as CD3+ and CD4+, in the lung and gut were detected after the interventions.
The FVC, FEV0.3, FEV0.3/FVC ratio, sIgA in the lung and gut, as well as expression level of CD3+ in the lung, showed a trend of successive decrease across control group, COPD group, and AECOPD group (P<0.05) . The above-mentioned parameters were lower in AECOPD group than those of Western Medicine group or integrated Chinese and Western Medicine group (P<0.05) . And they were lower in Western Medicine group than those of integrated Chinese and Western Medicine group (P<0.05) .
Integrated Chinese and Western Medicine treatment may improve immunity of the rat model via repairing the immune barrier function of the lung and gut by increasing the expression of sIgA, CD3+, and CD4+ in the lung and gut, which provides evidence for the prevention and treatment of COPD with Chinese medicine.
The Value of Handheld COPD-6 Spirometry for Early COPD Detection in High Risk Elderly Population in Community
Chronic obstructive pulmonary disease (COPD) is a common chronic disease of the respiratory tract, and lung function is necessary for the diagnosis of COPD. However, conventional pulmonary function meters are not suitable for a large number of physical examinations in the community. In recent years, it is recommended to use spirometry for COPD screening and management both at home and abroad. However, there is still a lack of relevant data on its consistency and effectiveness with conventional lung function.
To explore the value of handheld COPD-6 spirometry for early COPD detection in high risk elderly population in community.
From January 2018 to December 2019 at Dongshan Community Health Service Center, Jiangning District, Nanjing City, a free physical examination was performed on the elder population over 60 years who had high risk factors of COPD. Handheld COPD-6 spirometry was performed pre- and post-bronchodilator, the forced expiratory volume in one second (FEV1) , the forced expiratory volume in one second as a percentage of the predicted value (FEV1%prep) , the forced expiratory volume in six second (FEV6) , the percentage of forced expiratory volume in six second to the predicted value (FEV6%prep) , and the value of FEV1/FEV6 were evaluated and recorded. With FEV1/FEV6<80% as the initial screening positive pre-bronchodilator, retests were performed both with handheld COPD-6 spirometry and confirmatory spirometry after inhaling bronchodilator. Using FEV1/Forced vital capacity (FVC) <70% as the gold standard by confirmatory spirometry, receiver-operator characteristic (ROC) curve analysis was used to obtain the best diagnostic threshold of FEV1/FEV6. Sensitivity, specificity, positive predictive value, and negative predictive value were used to evaluate the diagnostic value of the handheld COPD-6 spirometer.
Out of the 382 participants, COPD was confirmed in 75 according to FEV1/FVC<70% post-bronchodilator. There was no statistically significant difference between FEV1%pred pre- and post-bronchodilator by handheld COPD-6 spirometry (t=-0.971, P=0.703) ; There was no statistically significant difference among FEV1%pred in two tests (t=-2.352, -1.429; P=0.396, 0.058) . The FEV1%pred detected by handheld COPD-6 spirometry post-bronchodilation was positively correlated with confirmatory spirometry (r=0.969, P<0.05) . Compared with FVC%pred and FEV6%pred post-bronchodilation, the difference was statistically significant (t=-3.170, P=0.005) ; and the FEV6%pred was positively correlated with the FVC%pred (r=0.653, P<0.05) . There was no statistically significant difference between FEV1/FEV6 and FEV1/FVC post-bronchodilation (t=1.735, P=0.084) ; and there was substantial agreement between the two diagnostic (r=0.871, P<0.05) . The FEV1/FEV6 cut-off with the greatest sum of sensitivity and specificity was 71% pre-bronchodilator, the sensitivity, specificity, positive and negative predictive values were 80.0%, 79.2%, 90.6% and 48.5% respectively. The greatest sum of sensitivity and specificity was 75% post-bronchodilator, the sensitivity, specificity, positive and negative predictive values were 80.0%, 98.8%, 98.4% and 58.3% respectively.
It is feasible to use FEV1/FEV6 as an indicator to screen COPD patients in elderly high-risk populations. It is recommended to use FEV1/FEV6<71% before bronchodilation and FEV1/FEV6<75% after diastole as the screening criteria.
Prediction Methods of Exercise Induced Desaturation Detected by Six-minute Walk Test in Patients with Stable Chronic Obstructive Pulmonary Disease
Exercise-induced desaturation (EID) is highly prevalent, and associated with the prognosis in patients with chronic obstructive pulmonary disease (COPD) . Current predicators of EID mostly depend on pulmonary function, and the assessment for their values is different.
To explore simple, and accurate methods suitably used in primary care to predict EID by six-minute walk test (6MWT) in patients with stable COPD.
A retrospective study was conducted. Participants were 67 stable COPD patients with respiratory clinic follow-ups selected from China-Japan Friendship Hospital from 2019 to 2020. Data were collected, including assessment results of pulmonary function test, 6MWT, modified Medical Research Council (mMRC) , and COPD Assessment Test (CAT) , as well as calculated BODE index. EID in 6MWT was defined as the difference between minimum oxygen saturation in 6MWT and resting oxygen saturation at the beginning of 6MWT (ΔSpO2) ≥4%. mMRC score, CAT score and BODE index were compared between patients with and without EID in 6MWT to estimate the association of ΔSpO2 in 6MWT with mMRC score, CAT score and BODE index. ROC analysis was used to estimate the predictive value of mMRC score, CAT score and BODE index for inducible hypoxia in 6MWT.
The ΔSpO2 in 6MWT was significantly negatively correlated with mMRC score (r=-0.492, P<0.001) , CAT score (r=-0.447, P<0.001) , and BODE index (r=-0.415, P<0.001) . The AUC of mMRC score in predicting EID in 6MWT was 0.683 (with 2 as the optimal cut-off value) , and that for CAT score was 0.765 (with 14 as the optimal cut-off value) , for BODE index was 0.711 (with 2 as the optimal cut-off value) .
All of mMRC score, CAT score and BODE index can be used to predict EID in 6MWT in patients with stable COPD.
Using Machine Learning to Build an Early Warning Model for the Risk of Severe Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease
The degree of airflow limitation is a key indicator of the progression degree in COPD patients. However, problems such as contraindications to testing and compliance make it difficult for some patients to undergo the relevant tests and evaluate the severity of the disease.
To develop and evaluate a machine learning algorithm-based early warning model for the risk of severe airflow limitation in COPD patients.
A cross-sectional design was used to investigate COPD inpatients in a tertiary hospital in Sichuan Province from 2019-01 to 2020-06. General clinical indexes and pulmonary function test data were collected. The data were randomly divided into training and test sets in the ratio of 8∶2, and 216 risk warning models were constructed in the training set using four missing value filling methods, three feature screening methods, 17 machine learning and one integrated learning algorithm. The area under the ROC curve (AUC) , accuracy, precision, recall and F1 score were used to evaluate the predictive performance of the model; and the ten-fold cross-validation method and Bootstrapping were used for internal and external validation, respectively. The test set data was used for model testing and selection, the posterior method was used for sample size verification.
A total of 418 patients were included, of which 212 (50.7%) patients were at risk of severe airflow limitation. After four missing value treatments and three feature filters, a total of 12 processed datasets and the importance ranking of 12 factors affecting airflow limitation were obtained, and the results showed that modified medical research council dyspnea scale grade (mMRC) , age, body mass index (BMI) , smoking history (yes, no) , chronic obstructive pulmonary disease assessment test (CAT) score, and dyspnea (yes, no) were at the forefront inthe ranking of variable features and were key indicators for constructing the model, which had an important role in predicting the outcome. Using unfilled, Lasso screening, mMRC grade, smoking history (yes, no) , and dyspnea (yes, no) were the top 3 predictors, with mMRC grade accounting for 54.15% of feature importance. In which, using unfilled, Boruta screening, CAT score, age, and mMRC class were the top 3 predictors, and CAT score accounted for 26.64% of feature importance. A total of 216 prediction models were obtained using 17 machine learning algorithms and 1 integrated learning for each of the 12 datasets. 17 machine learning algorithms with 10-fold cross-validation showed that the differences were statistically significant (P<0.05) when comparing the prediction performance of different algorithms, and the average AUC of the stochastic gradient descent algorithm was maximum (0.738±0.089) . The results of external validation of the test set using the Bootstrapping algorithm showed that the differences were statistically significant (P<0.05) when comparing the prediction performance of the models obtained by different algorithms, and the average AUC of the integrated learning algorithm was maximum (0.757±0.057) . Evaluation of the prediction performance of four missing value treatments and three feature filters using the Bootstrapping algorithm showed that the performance of the model was improved when no padding and Lasso filtering were applied, with a statistically significant difference (P<0.05) . Using the test set data for 216 machine learning models, the best model had an AUC of 0.790 9, accuracy of 75.90%, precision of 75.00%, recall of 78.57%, and F1 value of 0.767 4. The sample size validation results suggested that the study sample size can meet the modeling needs.
In this study, a risk warning model for severe airflow limitation in COPD patients was developed and evaluated. mMRC class, age, BMI, CAT score, presence of smoking history and dyspnea were the key indicators affecting airflow limitation. The model has good predictive effect and has potential clinical application.
