Profiles of Cough and Associated Risk Factors in Nonhospitalized Individuals With SARS-CoV-2 Omicron Variant Infection: Cross-Sectional Online Survey in China.

BACKGROUND: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. OBJECTIVE: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. METHODS: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. RESULTS: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). CONCLUSIONS: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.

Percent Recovery Index Predicts Poor Asthma Control and Exacerbation in Adults.

Background: Previous studies indicate that the percent recovery index (PRI: the percentage increase from the maximally reduced FEV1 after bronchodilator inhalation), one of the indexes of methacholine bronchial provocation, may predict acute asthma exacerbations in childhood and elderly asthmatics. It is known that childhood (<12) and elder (>60) asthmatics may be different to adult patients in many aspect including prognosis. However, in adults, a research for predicting value of PRI to exacerbation is still absence. Besides exacerbation, predicting value of PRI to poor asthma control is also unknown. We try to detect whether PRI can predict poor asthma control and exacerbation in adults in this research. Meanwhile, we try to detect whether treatment can influence PRI. Methods: In 61 adults with asthma, baseline PRI was measured during enrollment. And then baseline PRI was evaluated as a predictor of exacerbation or poor asthma control at an upcoming 3-month follow-up. The covariates included age, sex, BMI, previous exacerbation, smoking status and baseline lung function. After treatment for 3 months, PRI was measured again and compared with baseline PRI. Results: After the 3-month follow-up, we found that baseline PRI was significantly related to asthma exacerbation (P = 0.023), poor asthma control (ACT at 3 months, P = 0.014), decreased quality of life (decrease of MiniAQLQ, P = 0.010) and cumulative number of EDHO at 3 months (P = 0.039). Meanwhile, no significant correlation was observed between baseline PRI and inflammation factors (FENO, CaNO, and EOS). Finally, PRI was dramatically reduced after standard treatment for 3 months. Conclusion: PRI is efficient in the prediction of poor asthma control and exacerbation in adults. The predictive value of PRI may rely on the inherent property of asthmatic airway smooth muscle (ASM) independent of inflammation factors. Effective treatment can alleviate PRI dramatically and that indicate PRI may also be valuable in evaluation of curative effect.

Efficacy and safety of adjunctive nebulized colistin sulfate for multidrug-resistant Gram-negative bacteria pneumonia: a retrospective comparative cohort study.

BACKGROUND: The incidence of multidrug-resistant Gram-negative bacteria (MDR-GNB) pneumonia has increased in the last decade. If antibiotics are given only through intravenous, the antibiotic concentrations in lung tissue will be insufficient. Recently, nebulized antibiotics have shown effectiveness as an adjunctive therapy with intravenous antibiotics for resistant strains. Therefore, the goal of this study was to assess the efficacy and safety of adjunctive nebulized colistin sulfate in combination with intravenous antibiotics in patients with MDR-GNB pneumonia. METHODS: A total of 203 patients who were infected with MDR-GNB pneumonia were selected. Based on whether patients received nebulized colistin sulfate, patients were divided into 2 groups: the NCIA group (nebulized colistin sulfate in combination with intravenous antibiotics) and the IA group (intravenous antibiotics without nebulized colistin sulfate). After propensity score matching (PSM) analysis, we compared the efficacy in terms of favorable clinical outcomes, the bacteria detection rate, days of hospital stay, days of intensive care unit (ICU) stay, days of mechanical ventilation (MV), antipyretic time, days of antibiotic therapy, and 28-day all-cause mortality. Safety was also compared between groups. RESULTS: A total of 116 patients met the criteria for evaluation, with 46 patients in the NCIA group and 70 patients in the IA group. After PSM, 31 patients were selected from each group. There were significant differences in favorable clinical outcomes on days 7 (67.7% vs. 32.3%, P=0.005) and 14 (71% vs. 41.9%, P=0.045) and the bacteria detection rate on days 7, 14, and the last day. There were also significant differences in days of hospital stay (17 vs. 23 days, P=0.01), antipyretic time (0.5 vs. 7.5 days, P=0.037), and days of antibiotic therapy (14 vs. 23 days, P=0.002). However, there were no significant differences in days of ICU stay, days of MV, and 28-day all-cause mortality. For nephrotoxicity, the NCIA group did not increase the risk of acute kidney injury (16.1% vs. 9.7%, P=0.707), only one patient (3.2%) in the NCIA group developed airway hyperresponsiveness (P=1.000). CONCLUSIONS: For MDR-GNB pneumonia, nebulized colistin sulfate as an adjuvant supportive treatment for intravenous antibiotics maybe can improve clinical efficacy and has high safety.

Adjunctive use of prednisolone in the treatment of free-flowing tuberculous pleural effusion: A retrospective cohort study.

BACKGROUND: Adjunctive use of corticosteroids with anti-tuberculosis (TB) therapy has been reported to benefit people with tuberculous pleural effusion (TPE), while there is a paucity of data to support it as routine use. TPE can be subdivided into free-flowing type and loculated type. We evaluated the effects of adjunctive prednisolone therapy on functional sequelae, pleural thickening and pleural adhesions in patients with free-flowing TPE. METHODS: This is a retrospective cohort study, conducted from Jan 2013 to Dec 2016 (ChiCTR-ORC-16009267). All the patients were diagnosed with TPE, and treated with standard 4-drug anti-TB chemotherapy regimen and complete drainage of the effusion. We compared the incidence of a composite of roentgenographic sequelae (pleural thickening of > 2 mm, or pleural adhesions and costophrenic angle > 90°), or restrictive functional sequelae (FVC/FVC pre or TLC/TLC pre < 80%) between those who received adjunctive prednisolone therapy and those who did not. RESULTS: The final cohorts consisted of 135 subjects. Of those, 56 received adjunctive prednisolone therapy and 79 did not. The incidence of a composite of roentgenographic sequelae or restrictive functional sequelae was significantly decreased in the prednisolone group as compared with the control group (51.8% vs. 75.9%; RR 2.83, 95% confidence interval, 1.27-6.31, P = 0.011). No serious side effects due to corticosteroid were noted. CONCLUSIONS: This study detected a significant association between adjunctive prednisolone therapy and decreased incidence of a composite of radiographic sequelae, or functional sequelae in HIV-negative, free-flowing type TPE patients treated with adjunctive prednisolone.

Self-reported reasons for treatment non-adherence in Chinese asthma patients: A 24-week prospective telephone follow-up study.

BACKGROUND: Treatment non-adherence is a challenge to achieve asthma control. However, few prospective studies were done for exploring asthma patient adherence in real world. OBJECTIVES: To evaluate treatment adherence and causes of non-adherence in a large asthma Chinese population. To analyze newly-diagnosed patients' adherence first time. METHODS: About 1582 asthma patients' data were collected from 12 study centers in China from February, 2012 to October, 2012. Disease and treatment information of subjects were collected were at first clinic visit, at 4, 12, and 24 weeks after that, follow-up phone calls were carried out for recording subjects' treatment adherence based on their self-reports. Subjects who reported non-adherence were additionally asked to choose the primary non-adherence cause from a list of nine potential causes. RESULTS: Treatment adherence rate of all subjects markedly decreased from 83.3% at week 4 to 42.0% at week 24 after the first clinic visit. Significantly, at week 24, good treatment adherence rate in newly-diagnosed patients was lower than those patients with asthma history (22.9% vs. 63.9%, P < .001). Newly-diagnosed patients were three times more likely to become non-adherence than those patients with asthma history. Female patients had lower treatment adherence rate than male patients (38.3% vs. 45.6%, P = .006). Subjects in 30-39 year age group had the worst treatment adherence (27.3%). The most commonly chosen cause for non-adherence was "relief of symptoms after short-term controller medication use" (43.8%). CONCLUSIONS: Asthma patients' treatment adherence could be improved by improving patient education, doctor/patient partnership, and level of medical service in Chinese population.

Disease knowledge level is a noteworthy risk factor of anxiety and depression in patients with chronic obstructive pulmonary disease: a cross-sectional study.

BACKGROUND: Risk factors of anxiety and depression symptoms in patients with chronic obstructive pulmonary disease (COPD) have been widely researched, but most of them cannot be addressed clinically. The aim of this study was to investigate whether COPD knowledge level is a risk factor of anxiety and/or depression in COPD patients in addition to functional capacity and quality of life, and to determine the key topics of COPD knowledge. METHODS: A total of 364 COPD patients from four centers were recruited into this cross-sectional survey. Subjects' general medical information, assessments of lung function, dyspnea, quality of life, and exercise capacity, and responses to the Hospital Anxiety and Depression Scale (HAD) and the Bristol COPD Knowledge Questionnaire (BCKQ) were collected. Partial correlation analysis was performed, and a multivariable model testing risk factors of anxiety and depression as well as a multivariable model of 13 topics of knowledge derived from BCKQ were constructed. RESULTS: Subjects with anxiety or depression were more likely to have less COPD knowledge. Partial correlation analysis revealed that HAD score was negatively correlated with BCKQ score (rho = -0.153, P = 0.004). BCKQ score was significant in the multivariable model that tested risk factors of anxiety and depression (P = 0.001, OR = 0.944). Topics of epidemiology (P < 0.001, OR = 0.653) and infections (P = 0.006, OR = 0.721) were significant in the multivariable model evaluating 13 topics. CONCLUSIONS: The level of patients' disease knowledge is a significant risk factor of anxiety and depression in COPD patients. Epidemiology and infections are key topics of COPD knowledge to target in the Chinese population. TRIAL REGISTRATION: ChiCTR-OCS-12002518.

The effects and mechanism of ginsenoside Rg1 on myocardial remodeling in an animal model of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Recent studies haveshown that ginsenoside Rg1, extracted from the dry roots of Panax notoginseng as a traditional Asian medicine, plays an anti-fibrosis role in myocardial remodeling. However, the mechanism still remains unclear. In the present study, we investigate the effect of ginsenoside Rg1on the collagenic remodeling of myocardium in chronic thromboembolic pulmonary hypertension (CTEPH), and its potential mechanism. METHODS: A rat model of CTEPH was established by injecting thrombi through the jugular vein wice in2 weeks. Four weeks later, four groups (Group A: normal rats + normal saline; Group B: normal rats + Rg1; Group C: CTEPH model + normal saline; Group D: CTEPH model + Rg1) were established. Normal saline and Rg1 were administrated by intraperitoneal injection. Ineach group, we measured the hemodynamic parameters, as well as the right ventricle to left ventricle (RV/LV) thickness ratio. Myocardial tissue sections of the RV were stained by hematoxylin-eosin +gentian violet and the morphological characteristics were observed by light microscopy. The matrix metalloproteinases (MMP) -2 and -9 were detected by the western blot. RESULTS: Compared with Group A and Group B, the right ventricular systolic pressure was significantly increased in Group C and significantly decreased in Group D. Compared with Group A and Group B, the RV/LV thickness ratio of the rats was significantly higher in Group C and Group D. There was significant fibrosis with collagen in Group C compared with Group A and Group B, and less significant changes in Group D were observed compared with those in Group C. The expression of MMP-2 and MMP-9 exhibited a significant decrease in Group C and was also significantly decreased in Group D compared withGroup A and Group B. Also, a negative linear relationship was shown between collagen-I and the expression of MMP-2 and MMP-9. CONCLUSIONS: Our animal study showed that ginsenoside Rg1 positively affects myocardial remodeling and pulmonary hemodynamics in CTEPH. Upregulation of the expression of MMP-2 and MMP-9 could explain the beneficial effects of ginsenoside Rg1 in CTEPH.

Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB.

BACKGROUND: Nuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro. METHODS AND RESULTS: In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1ß in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKß/total IKKß, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro. CONCLUSIONS: These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKß activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.

Addition of theophylline or increasing the dose of inhaled corticosteroid in symptomatic asthma: a meta-analysis of randomized controlled trials.

PURPOSE: Low-dose theophylline has anti-inflammatory effects. The aim of this study was to evaluate the effects of adding theophylline compared with increasing the dose of inhaled corticosteroid (ICS) on symptomatic asthma. MATERIALS AND METHODS: The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. The extracted data were further analyzed by a meta-analysis. RESULTS: Four randomized, controlled, parallel studies were selected. Addition of theophylline produced a greater increase of forced expiratory volume in one second as %predicted (FEV1pred) by 2.49% [95% confidence interval (CI) 1.99-3.00; z = 9.70; p < 0.001], compared with increasing the dose of ICS. There was no difference between the two treatments in terms of peak expiratory flow (PEF). CONCLUSION: Addition of theophylline to ICS has similar therapeutic effects on improving lung function as increasing the dose of ICS in the treatment of symptomatic asthma.

[Morphological investigation of the protective effect of astragaloside preconditioning against ischemia-reperfusion lung injury in rats].

OBJECTIVE: To study the protective mechanisms of the astragaloside against ischemia-reperfusion lung injury in rats. METHODS: Ischemia-reperfusion lung injury was induced in SD rats. Astragalus armour glucoside was dissolved in 1% of sodium carboxymethyl cellulose at different concentrations (8, 6, and 3 mg/ml) was intragastrically administered in the rats at the dose of 1 ml/100 g. Cellular and subcellular structural changes in the lung tissue were observed at the end of the experiment using optical and transmission electron microscope, with the wet/dry ratio of the lung tissue and myeloperoxidase (MPO) activity measured. RESULTS: The wet/dry ratio and myeloperoxidase activity in the lung tissue were significantly higher in the model group than in the sham-operated group (P<0.05), and were significantly lowered by the treatment with astragalus armour glucoside at different doses (P<0.01 or 0.05), and the effect was especially obvious in rats receiving a moderate dose. Pulmonary capillary expansion, erythrocyte leakage and exudate in the alveolar space with obvious pathological changes in the type I and II epithelial cells were observed in model group. Pulmonary capillary expansion was reduced in rats treated with high, medium and low dose of Astragalus armour glucoside, and the medium dose group showed the most obvious effect, in which no edema fluid in the alveolar space or erythrocyte leakage was found with also reduced type II lung epithelial cell degranulation. CONCLUSION: Astragaloside has obvious antioxidant effect in rats with ischemia-reperfusion lung injury, and a medium dose produces the best effect.

Comparison of inhaled corticosteroid combined with theophylline and double-dose inhaled corticosteroid in moderate to severe asthma.

OBJECTIVE: Recent studies have found that theophylline exerts anti-inflammatory and immunomodulatory effects. This study was performed to compare the efficacy of inhaled corticosteroids (ICS) combined with slow-release theophylline (SRT) with that of double-dose ICS in asthma control, anti-inflammatory activity and safety. METHODOLOGY: In a randomized, open, parallel, control trial, 41 patients with asthma were randomly treated with either beclomethasone dipropionate 500 microg b.i.d. (BDP group) or a combination of BDP 250 microg b.i.d and SRT 0.2 g b.i.d. (SRT/BDP group) for 6 weeks. At the start and at the end of treatment, lung function testing and sputum induction were performed, and plasma cortisol levels were measured. Sputum was analyzed for cell differential counts and the interleukin (IL)-5 level. Patients kept a record of peak expiratory flow (PEF), symptom score, and beta2-agonist use. RESULTS: Significant increases in the morning and the evening PEF and FEV1 were observed (P < 0.05), together with an obvious reduction in symptom score and beta2-agonist use (P < 0.01). Significant decreases in the percentage eosinophils and IL-5 level in induced sputum also occurred (P < 0.05). However, there was no difference between the two groups for all these parameters. There was no significant change in the plasma cortisol level for either group. CONCLUSIONS: Both ICS combined with SRT and double-dose ICS had the same effect on asthma control, improving symptoms and ameliorating lung function. Both therapies had similar anti-airway inflammatory effects and therapeutic safety. Combining SRT with ICS may allow a reduction in ICS dose when treating asthma.