Methods
Study design and population
This multicenter cross-sectional study was performed at respiratory departments of the Second Affiliated Hospital of Chongqing Medical University and the First People’s Hospital of Suining City from January 2019 to August 2020. This study was approved by the Research Ethics Committees of the Second Affiliated Hospital of Chongqing Medical University (No. 2019-23) and the First People’s Hospital of Suining City (NO. 2020-37) in accordance with the Declaration of Helsinki. The heights of the two hospitals were 305 meters and 801 meters above sea level, respectively. All AECOPD patients had no plateau living history. Informed consent was obtained from all the patients by the responsible physician or an appropriately trained staff member. Standard care and treatments were provided in our study according to current clinical guidelines [21,22].
Sample size determinations
As for sample size, a minimum amount of 246 (82 in each group) was required to detect at least a 20% difference in effect size for an 80% power, assuming α = 0.05 and allocation ratio = 1:1:1. Furthermore, 20% more (98 in each group) patients were recruited.
Inclusion and exclusion criteria
The inclusion criterion was an acute exacerbation of COPD requiring hospitalization with age ≥40 years [22,23]. Exclusion criteria were as follows: non-respiratory failure patients without lung function test; active pulmonary tuberculosis (TB); asthma; bronchiectasis; pneumoconiosis; interstitial lung diseases (ILDs); pulmonary edema; pulmonary embolism; other chronic lung diseases; dysphagia and aspiration; dementia; hospital-acquired pneumonia (HAP); antibiotics within the last 2 weeks; immunosuppressive status (immunosuppressive drugs in the previous 2 weeks, organ transplant, and/or HIV infection); system steroid use within the last 2 weeks; the history of malignant diseases; renal failure; and liver failure. A total of 598 patients with hospitalized AECOPD were enrolled. And 169 were excluded. In the end, 111 patients were <7 days of LHS (Normal LHS, N-LHS), 218 patients were 7-10 days of LHS (Mild Prolonged LHS, MP-LHS), and 100 patients were ≥11 days of LHS (Severe Prolonged LHS, SP-LHS) (Figure 1).
Definitions
According to Global Initiative for Chronic Obstructive Lung Disease (GOLD) [22], the diagnosis of COPD was confirmed by the pulmonologists, based on noxious stimuli exposure history, risk elements, clinical symptoms, and spirometry (FEV1/FVC% <0.7 after bronchodilator inhalation). AECOPD was defined as an event in the natural course of the disease characterized by acute changes in clinical symptoms beyond normal day-to-day variation, resulting in additional therapy [22-24]. Chronic cor pulmonale (CCP) was defined as right ventricular hypertrophy resulting from the diseases affecting the function and/or structure of the lungs except when these pulmonary alterations were the result of diseases that primarily affect the left side of the heart [25,26]. And, the diagnosis of CCP was based on the findings of clinical presentations, echocardiography, and electrocardiogram (ECG) [25,26]. The ex-smoker was defined as abstaining from smoking ≥ for 6 months. Neutrophils-to-lymphocytes ratio (NLR) was defined as neutrophils divided by lymphocytes in blood [24].
Data collection
In our study, demographic data, underlying diseases, comorbidities, symptoms, and the length of hospital stay (LHS) were recorded and collected. The blood samples for laboratory tests and lung function tests were all collected and performed within 24h after admission. However, for the safety and cooperation concerns, a spirometer test wasn’t performed in patients with respiratory failure. All patients underwent computed tomography (CT) scans within 48h after admission. And the results were reviewed by one independent radiologist and one pulmonologist in each hospital, who were blinded to the study. Discrepancies were settled by consensus.
Statistical analysis
Data were analyzed using SPSS 20.0 software (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as the Mean ± standard deviation (SD), and categorical data were expressed as frequencies. The data distribution was examined by the Kolmogorov-Smirnov test. Continuous variables with normal distribution were analyzed by one-way ANOVA with LSD and SNK’s posthoc trial. Continuous variables with abnormal distribution and ordinal variables were measured by the Kruskal-Wallis H test. The Chi-square test was used to analyze categorical variables. Collinearity diagnostic was applied for selected variables before the regression model was built. Multiple logistics regression was performed to investigate the independent risk factors associated with LHS in AECOPD patients [24]. A threshold of p< 0.05 was thought to be significant.