One-Year Temporal Changes in Long COVID Prevalence and Characteristics: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study aimed to explore the 1-year temporal change in prevalence, variety, and potential risk factors of long COVID symptoms and to further predict the prognostic trends of long COVID. METHODS: We searched electronic databases for related studies published from January 2020 to February 2022 and conducted 1-group meta-analysis and locally weighted regression to explore the monthly temporal change in the prevalence of each long COVID symptom in 1-year follow-up period. RESULTS: A total of 137 studies were included in meta-analysis, including 134 093 participants. The temporal change of any long COVID symptom showed a steep decrease initially (from 92% at acute phase to 55% at 1-month follow-up), followed by stabilization at approximately 50% during 1-year follow-up. Six months or more after the acute phase, the odds ratio of population characteristic-related factors increased, such as female (from 1.62 to 1.82), whereas the odds ratio value of acute phase-related factors (severe or critical cases and hospitalization) decreased. As for specific symptoms, approximately two-thirds of the symptoms did not significantly reduce during the 1-year follow-up, and the neuropsychiatric symptoms showed a higher long-term prevalence (approximately 25%) and longer persistence than physical symptoms. CONCLUSIONS: The temporal changes in the prevalence and characteristics speculate that long COVID may persist longer than expected. In particular, we should pay more attention to neuropsychiatric symptoms and other symptoms for which there is no significant downward trend in prevalence. The influence of acute phase-related factors for long COVID gradually decreases over time, whereas the influence of population characteristic-related factors gradually increases.

Humoral responses after inactivated COVID-19 vaccination in individuals with and without prior SARS-CoV-2 infection: A prospective cohort study.

We evaluated and compared humoral immune responses after inactivated coronavirus disease 2019 (COVID-19) vaccination among naïve individuals, asymptomatically infected individuals, and recovered patients with varying severity. In this multicenter, prospective cohort study, blood samples from 666 participants were collected before and after 2 doses of inactivated COVID-19 vaccination. Among 392 severe acute respiratory syndrome coronavirus 2-naïve individuals, the seroconversion rate increased significantly from 51.8% (median antispike protein pan-immunoglobulins [S-Igs] titer: 0.8 U/ml) after the first dose to 96% (median S-Igs titer: 79.5 U/ml) after the second dose. Thirty-two percent of naïve individuals had detectable neutralizing antibodies (NAbs) against the original strain but all of them lost neutralizing activity against the Omicron variant. In 274 individuals with natural infection, humoral immunity was significantly improved after a single vaccine dose, with median S-Igs titers of 596.7, 1176, 1086.5, and 1828 U/ml for asymptomatic infections, mild cases, moderate cases, and severe/critical cases, respectively. NAb titers also improved significantly. However, the second dose did not substantially increase antibody levels. Although a booster dose is needed for those without infection, our findings indicate that recovered patients should receive only a single dose of the vaccine, regardless of the clinical severity, until there is sufficient evidence to confirm the benefits of a second dose.

Using Virtual Reality Exposure Therapy in Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: This study aimed to assess the effectiveness of virtual reality (VR) in managing different types of pain in different age groups and to provide evidence for the clinical application of new alternative strategy for pain management. METHODS: Electronic databases, including the Cochrane Library, PubMed, EMBASE, and the Web of Science, were searched for studies published up to October 2020. Randomized controlled trials that reported on VR for pain management were included. RESULTS: A total of 31 randomized controlled trials were included. As for the pain intensity, the increase of visual analog scale score in the VR group was 1.62 scores less than that in the control group. In juvenile patients, the VR group had 1.79 scores lower than that in control group. For adult patients, the VR group had 1.34 scores lower than that in control group. As for other pain-related indicators, the VR group had lower levels of anxiety, lower pain unpleasantness, lower pulse rate, and shorter duration of dressing change and spent less time thinking about pain. Nevertheless, there was no statistical difference in pain tolerance. VR can effectively alleviate acute pain. In terms of chronic low back pain and cancer-related pain, there was no statistical difference between VR therapy and standard therapy. CONCLUSIONS: VR is a feasible alternative therapy for both juveniles and adults in pain management, and it has a greater potential for juveniles. VR can effectively alleviate acute pain. Nevertheless, VR showed little effectiveness in increasing pain tolerance, which may explain in part the ineffectiveness of VR therapy in pain management for chronic pain.

Assessment of comorbidities and prognosis in patients with COPD diagnosed with the fixed ratio and the lower limit of normal: a systematic review and meta-analysis.

BACKGROUND: Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) is not uniform, COPD guidelines recommend fixed ratio (FR), whereas ATS and ERS define airflow obstruction based on lower limit of normal (LLN). We aim to determine if there is difference between the two diagnostic criteria for morbidity, mortality, exacerbation. METHODS: Four databases and all relevant studies from the references were searched from inception to June 25, 2019, to find studies that described the rate of comorbidity, the exacerbation rates, mortality in COPD patients. Data analysis was performed using STATA/SE 14.0 and followed the standard of Cochrane Collaboration. A sensitivity analysis was performed to find the source of heterogeneity. RESULTS: Thirteen studies and 154,447 participants were finally included in this meta-analysis. The 11 cohort studies and 2 cross-sectional studies were all high-quality. Patients with airflow limitation according to either FR or LLN had higher mortality (HRFR+/LLN- = 1.27, 95% CI = 1.14-1.42; HRFR-/LLN+ = 1.83, 95% CI = 1.17-2.86) than those who met neither criteria. When compared with the FR-/LLN- criteria, those who met the FR criteria were more likely to exacerbate (HR FR+/LLN- = 1.64, 95% CI = 1.09-2.46; HR FR-/LLN+ = 1.58, 95% CI = 0.70-3.55). The meta-analysis for comorbidities showed no significant difference between patients who met neither criteria and those who met LLN or FR criteria. CONCLUSION: The patients with airflow limitations according to FR were more likely to exacerbate than those with LLN only. Patients that met either FR or LLN were more likely to have higher mortality than FR-/LLN-. There was no difference between the FR+/LLN- and FR-/LLN+ groups for the occurrence of comorbidities.

Topical Application of Keratinocyte Growth Factor Conjugated Gold Nanoparticles Accelerate Wound Healing.

Keratinocyte growth factor (KGF) has been demonstrated to specifically stimulate the multiplication and migration of keratinocytes. However, due to rapid degradation, the results of topical application of growth factors on wounds are unsatisfactory. In this study, we cross-linked KGF to the surface of gold nanoparticles (GNPs) and explored their effects on wound healing. The as-synthesized nanocomposite (KGF-GNPs) displayed good colloidal stability, decent biocompatibility as well as negligible cellular cytotoxicity. The in vitro cellular experimental results demonstrated that KGF-GNPs could effectively promote the proliferation of keratinocytes in contrast to bare GNPs or KGF. Furthermore, in animal full-thickness wound model, KGF-GNPs are more conducive to wound healing than bare GNPs or KGF. KGF-GNPs enhanced wound healing by promoting wound re-epithelialization rather than granulation. The superior biocompatibility, colloidal depressiveness and biological activity of this nanocomposite indicate that it could be utilized as a promising wound healing drug for clinical application in the future.

An effectiveness study of vaccination and quarantine combination strategies for containing mpox transmission on simulated college campuses.

The ongoing transmission of mpox in specific countries and regions necessitates urgent action. It is essential to implement targeted containment strategies that concentrate on high-risk populations and critical locations, such as college campuses, to effectively curb the spread of mpox. This study is dedicated to evaluating the performance of various vaccination and quarantine strategies in curbing the spread of mpox and estimating the outbreak risk. To accomplish this, we constructed a stochastic, agent-based, discrete-time susceptible-latent-infectious-recovered (SLIR) model, to examine mpox transmission on a simulated college campus. Our findings reveal that relying solely on PEP is insufficient in containing mpox effectively. To bolster the population immunity and protect the vulnerable, pre-exposure vaccination among high-risk populations prior to an outbreak is imperative. Our study demonstrates that a pre-exposure vaccination rate of 50% in high-risk populations can led to a remarkable 74.2% reduction of infections. This translated to a mere 1.0% cumulative infection incidence in the overall population. In cases where the desired vaccination coverage is not attainable, enhancing case detection and isolation measures can serve as an effective emergency response to contain mpox outbreaks. For pre-exposure vaccination coverage of 20% or lower, a 40% isolation ratio is necessary to keep the cumulative number of infections in check. However, when the coverage exceeds 30%, a reduced isolation ratio of 20% becomes sufficient to manage the outbreak effectively. These insights underscore the importance of strategic pre-exposure vaccination in conjunction with robust surveillance and isolation protocols to safeguard public health and prevent the escalation of mpox outbreaks.

Pathogen characteristics of respiratory infections in the season after the COVID-19 pandemic between August and December 2023: evidence from direct-to-consumer testing-based surveillance in Guangzhou and Beijing, China.

OBJECTIVES: In the fall-winter of 2023, China experienced its first epidemic season of respiratory diseases since the COVID-19 pandemic. Gathering timely data about pathogenetic characteristics of respiratory infections is crucial to complement current respiratory surveillance mechanisms in China. Data from direct-to-consumer (DTC) multi-respiratory pathogen (MRP) testing could serve as a novel source of multi-pathogen data for community-based surveillance. METHODS: A pioneering initiative was launched to detect multiple respiratory pathogens in Beijing and Guangzhou, China. DTC MRP tests were used to provide proactive surveillance ahead of medical services. RESULTS: A total of 28,018 participants were enrolled between 22 August and 10 December 2023. Positive findings for at least one respiratory pathogen were observed in 26,202 (93.5%) participants. Influenza virus A, respiratory syncytial virus (RSV), and human adenovirus are the three leading viral pathogens detected with proportions of 18.0%, 10.6%, and 8.8%. Viral-bacterial pathogens were co-detected in 9736 (34.7%) of participants, which reduced to 22.2% for bacterial-bacterial co-detection, and 22.0% for bacterial mono-detection. The epidemiological ecology of respiratory pathogens within both viral clusters and specific pathogens varied among cities. The peak of RSV epidemics in Guangzhou occurred in the fall of 2023, earlier than in Beijing. CONCLUSION: The innovative program offered enhanced surveillance capabilities beyond traditional methods, enabling prompt feedback about test results and mitigating the risk of cross-infection caused by waits in healthcare facilities.

A Large-Scale Online Survey on Clinical Severity and Associated Risk Factors for SARS-CoV-2 Omicron Infection - China, April-May 2023.

What is already known about this topic?: Individuals who initially contract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lack significant mixed immunity. Therefore, it is crucial to monitor the clinical characteristics and associated factors of these individuals in order to inform policy-making. What is added by this report?: The common symptoms reported were fever, cough, and sore throat. Reinfections and receiving four vaccination doses within a 6-month period were found to be associated with a shorter duration of virus shedding, decreased hospitalization rate, and reduced risk of pneumonia. Individuals aged 60 years and older, as well as those with underlying medical conditions, had a higher risk of developing pneumonia. What are the implication for public health practices?: Online surveys conducted through social media platforms have the potential to complement disease surveillance and data collection efforts. In terms of vaccination prioritization, it is recommended to prioritize older individuals and those with underlying diseases.

Mapping the Characteristics of Respiratory Infectious Disease Epidemics in China Based on the Baidu Index from November 2022 to January 2023.

Introduction: Infectious diseases pose a significant global health and economic burden, underscoring the critical need for precise predictive models. The Baidu index provides enhanced real-time surveillance capabilities that augment traditional systems. Methods: Baidu search engine data on the keyword "fever" were extracted from 255 cities in China from November 2022 to January 2023. Onset and peak dates for influenza epidemics were identified by testing various criteria that combined thresholds and consecutive days. Results: The most effective scenario for indicating epidemic commencement involved a 90th percentile threshold exceeded for seven consecutive days, minimizing false starts. Peak detection was optimized using a 7-day moving average, balancing stability and precision. Discussion: The use of internet search data, such as the Baidu index, significantly improves the timeliness and accuracy of disease surveillance models. This innovative approach supports faster public health interventions and demonstrates its potential for enhancing epidemic monitoring and response efforts.

Incidence, hospitalization, and mortality in children aged 5 years and younger with respiratory syncytial virus-related diseases: A systematic review and meta-analysis.

Objectives: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children. We aimed to analyze the factors affecting the estimation of RSV-related disease burden, and to provide evidence to help establish a surveillance system. Methods: We searched the English- and Chinese-language databases for articles published between January 1, 2010 and June 2, 2022. The quality of the included articles was assessed using the Agency for Healthcare Research and Quality scale. Random-effects models were used for data synthesis and subgroup analyses. This review was registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022372972). Results: We included 44 studies (149,321,171 participants), all of which were of medium or high quality. The pooled RSV-related disease incidence, hospitalization rate, in-hospital mortality, and overall mortality rates in children aged 5 years and younger were 9.0 per 100 children per year (95% confidence interval [CI]: 7.0-11.0), 1.7 per 100 children per year (95% CI: 1.3-2.1), 0.5 per 100 children per year (95% CI: 0.4-0.5), and 0.05 per 100 children per year (95% CI: 0.04-0.06), respectively. Age, economics, surveillance types, case definition, and data source were all recognized as influencing factors. Conclusions: A standardized and unified RSV surveillance system is required. Case definition and surveillance types should be fully considered for surveillance of different age groups.

Risk assessment for cross-border transmission of multi-country Mpox outbreaks in 2022.

OBJECTIVES: Global trade and travel have facilitated infectious disease transmission. In 2022, over a short time, cross-border Mpox (monkeypox) outbreaks were reported. Since, most countries are at risk of cross-border Mpox transmissions, in this study, we developed a real-time risk assessment model for the cross-border transmission of Mpox. METHODS: This model includes priori indicators related to the source area before the Mpox outbreak and posterior indicators derived from the quantitative data evaluation afterward. Based on transportation, this model can also be used to assess the global import risk of Mpox for specific countries and cities. RESULTS: European risk values displayed high levels between May and July 2022 and gradually decreased after July. After September 2022, risk values elevated in most countries and regions in the Americas. As for China, high importation risk cities were highly exposed to the United States and moderately exposed to Australia and Germany. Some cities were exposed to the potential risks from only one source country. CONCLUSIONS: Dynamic surveillance of the cross-border spread of infectious diseases is essential. Importation risks vary widely across cities and regions, and developing risk prevention and control strategies specific to the traffic flow, medical care capabilities, and risk levels in the main source countries are essential.

Quantitative Analysis of the Effectiveness of Antigen- and Polymerase Chain Reaction-Based Combination Strategies for Containing COVID-19 Transmission in a Simulated Community.

The number of coronavirus disease 2019 (COVID-19) cases continues to surge, overwhelming healthcare systems and causing excess mortality in many countries. Testing of infectious populations remains a key strategy to contain the COVID-19 outbreak, delay the exponential spread of the disease, and flatten the epidemic curve. Using the Omicron variant outbreak as a background, this study aimed to evaluate the effectiveness of testing strategies with different test combinations and frequencies, analyze the factors associated with testing effectiveness, and optimize testing strategies based on these influencing factors. We developed a stochastic, agent-based, discrete-time susceptible-latent-infectious-recovered model simulating a community to estimate the association between three levels of testing strategies and COVID-19 transmission. Antigen testing and its combination strategies were more efficient than polymerase chain reaction (PCR)-related strategies. Antigen testing also showed better performance in reducing the demand for hospital beds and intensive care unit beds. The delay in the turnaround time of test results had a more significant impact on the efficiency of the testing strategy compared to the detection limit of viral load and detection-related contacts. The main advantage of antigen testing strategies is the short turnaround time, which is also a critical factor to be optimized to improve PCR strategies. After modifying the turnaround time, the strategies with less frequent testing were comparable to daily testing. The choice of testing strategy requires consideration of containment goals, test efficacy, community prevalence, and economic factors. This study provides evidence for the selection and optimization of testing strategies in the post-pandemic era and provides guidance for optimizing healthcare resources.

Clinical manifestations of respiratory syncytial virus infection and the risk of wheezing and recurrent wheezing illness: a systematic review and meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) infection in infants is a global health priority. We aimed to investigate the common manifestations of RSV infection by age group and human development index (HDI) level and to assess its association with the development of wheezing and recurrent wheezing illness. METHODS: We searched the literature published between January 1, 2010 and June 2, 2022 in seven databases. Outcomes included common manifestations and long-term respiratory outcomes of RSV infection in children. Random- and fixed-effect models were used to estimate the effect size and their 95% confidence intervals. Subgroup analysis was conducted by age and HDI levels. This review was registered in PROSPERO (CRD42022379401). RESULTS: The meta-analysis included 47 studies. The top five manifestations were cough (92%), nasal congestion (58%), rhinorrhea (53%), shortness of breath (50%), and dyspnea (47%). The clinical symptoms were most severe in infants. In our analysis, compared to very high and high HDI countries, fewer studies in medium HDI countries reported related manifestations, and no study in low HDI countries reported that. The RSV-infected infants were more likely to develop wheezing than the non-infected infants [odds ratio (OR), 3.12; 95% CI, 2.59-3.76] and had a higher risk of developing wheezing illnesses after recovery (OR, 2.60; 95% CI, 2.51-2.70). CONCLUSIONS: Cough and shortness of breath are common manifestations of RSV infection. More attention should be given to infants and areas with low HDI levels. The current findings confirm an association between RSV infection and wheezing or recurrent wheezing illness.

Healthcare Workers' Attitudes toward Influenza Vaccination: A Behaviour and Social Drivers Survey.

This study aimed to understand the intention and correlation of receiving and recommending influenza vaccine (IV) among healthcare workers (HCWs) in China during the 2022/2023 season using the behavior and social drivers (BeSD) tools. A self-administered electronic survey collected 17,832 participants on a media platform. We investigated the willingness of IV and used multivariate logistic regression analysis to explore its associated factors. The average scores of the 3Cs' model were compared by multiple comparisons. We also explored the factors that potentially correlated with recommendation willingness by partial regression. The willingness of IV was 74.89% among HCWs, and 82.58% of the participants were likely to recommend it to others during this season. Thinking and feeling was the strongest domain independently associated with willingness. All domains in BeSD were significantly different between the hesitancy and acceptance groups. Central factors in the 3Cs model were significantly different among groups (p < 0.01). HCWs' willingness to IV recommendation was influenced by their ability to answer related questions (r = 0.187, p < 0.001) after controlling for their IV willingness and perceived risk. HCWs' attitudes towards IV affect their vaccination and recommendation. The BeSD framework revealed the drivers during the decision-making process. Further study should classify the causes in detail to refine HCWs' education.

Association between influenza vaccination and SARS-CoV-2 infection and its outcomes: systematic review and meta-analysis.

BACKGROUND: World Health Organization recommends that influenza vaccines should benefit as much of the population as possible, especially where resources are limited. Corona virus disease 2019 (COVID-19) has become one of the greatest threats to health systems worldwide. The present study aimed to extend the evidence of the association between influenza vaccination and COVID-19 to promote the former. METHODS: In this systematic review, four electronic databases, including the Cochrane Library, PubMed, Embase, and Web of Science, were searched for related studies published up to May 2022. All odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by meta-analysis. RESULTS: A total of 36 studies, encompassing 55,996,841 subjects, were included in this study. The meta-analysis for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provided an OR of 0.80 (95% CI: 0.73-0.87). The statistically significant estimates for clinical outcomes were 0.83 (95% CI: 0.72-0.96) for intensive care unit admission, 0.69 (95% CI: 0.57-0.84) for ventilator support, and 0.69 (95% CI: 0.52-0.93) for fatal infection, while no effect seen in hospitalization with an OR of 0.87 (95% CI: 0.68-1.10). CONCLUSION: Influenza vaccination helps limit SARS-CoV-2 infection and severe outcomes, but further studies are needed. REGISTRATION: PROSPERO, CRD42022333747.

Willingness toward COVID-19 vaccination, coadministration with other vaccines and receive a COVID-19 vaccine booster: a cross-sectional study on the guardians of children in China.

This study aimed to investigate the changes in the willingness of guardians to administer the COVID-19 vaccine to their children, allow the coadministration of other vaccines, and administer the COVID-19 vaccine booster dose. This was a follow-up study conducted 6 months after a similar previous study. The self-administered questionnaire was distributed through the "Xiao Dou Miao" app and 9424 guardians with access to this app participated in the survey that was conducted from September 15 to October 8, 2021. Of all the participating guardians, 86.68% were willing to vaccinate their children with the COVID-19 vaccine, which was approximately 16% more than those in our previous study. Guardians aged ≥40 years, healthcare workers, and those with children aged ≥3 years were more willing to vaccinate their children. Approximately 77% of the guardians were willing toward the coadministration of COVID-19 and influenza vaccines. Approximately 64% of the guardians were willing toward the coadministration of other nonimmunization program vaccines with the COVID-19 vaccine for their children. The primary reasons for reluctance toward the coadministration of vaccines were concerns about vaccine safety and effectiveness. If necessary, 92% of the guardians were willing to receive a COVID-19 vaccine booster and 82% were willing to vaccinate their children with a COVID-19 vaccine booster. We hope that this research will facilitate the formulation of successful strategies for the implementation of COVID-19 vaccinations, covaccinations, and COVID-19 booster doses, particularly for children aged <6 years.

Long-term outcomes in COVID-19 patients who recovered from the first wave of the pandemic.

This cross-sectional study evaluated the long-term health effects of coronavirus disease 2019 (COVID-19) in Jianghan District (Wuhan, China). The results showed that 61.4% of COVID-19 patients reported at least one symptom and 8.8% had depressive symptoms at the 17-month follow-up. The proportion of patients with chest radiographic abnormalities in Fangcang shelter hospitals and designated COVID-19 hospitals was 31.6% and 41.1%, respectively, and the proportion of patients with impaired pulmonary diffusion capacity in these hospitals was 52.8% and 60.9%, respectively. Female sex (odds ratio [OR] = 1.48, 95% confidence interval [CI]: 1.16-1.88), severe disease (OR = 1.46, 95% CI: 1.01-2.10) and a higher number of initial symptoms (OR = 1.31, 95% CI: 1.23-1.40) were associated with the development of sequelae symptoms at 17 months. This study involving community-dwelling COVID-19 adults may help determine the long-term effects of COVID-19 during the first pandemic wave. Nonetheless, larger follow-up studies are needed to characterize the post-COVID-19 condition.

Efficacy and cardiovascular safety of LAMA in patients with COPD: a systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) is at present the third leading cause of death in the world. Long-acting muscarinic antagonist (LAMA) is widely used as a bronchodilator in patients with COPD. However, there is controversy concerning their cardiovascular safety. This meta-analysis aims to assess the efficacy and cardiovascular safety of LAMAs versus placebo in patients with COPD. We searched Pub Med, Embase, Cochrane Library, and Web of Science to identify studies that compared LAMA with placebo in patients with COPD. Twenty-one studies involving 24,987 participants were finally included in the analysis. There was no significant difference in the incidence of all adverse events (risk ratio (RR)=1.01, 95% CI 1.00 to 1.02, I2=15.2%) and cardiovascular events (RR=0.98, 95% CI 0.88 to 1.09, I2=4.9%) in patients treated with LAMAs versus placebo. LAMAs significantly improved trough forced expiratory volume in 1 s (weighted mean difference (WMD)=0.12, 95% CI 0.10 to 0.14, I2=86.6%), Transitional Dyspnea Index (WMD=0.75, 95% CI 0.56 to 0.94, I2=0%), and St. George's Respiratory Questionnaire (WMD=‒2.50, 95% CI ‒3.32 to ‒1.69, I2=39.8%). Moreover, LAMAs significantly reduced the incidence of exacerbation in patients with COPD (RR=0.85, 95% CI 0.79 to 0.91, I2=69.9%). LAMAs are safe therapy and play a pivotal role in improving lung function, dyspnea, and health status, and reducing the exacerbation in patients with COPD.

Low-dose theophylline in addition to ICS therapy in COPD patients: A systematic review and meta-analysis.

BACKGROUND: A synergism has been reported between theophylline and corticosteroids, wherein theophylline increases and restores the anti-inflammatory effect of inhaled corticosteroids (ICS) by enhancing histone deacetylase-2 (HDAC) activity. Several studies have explored the efficacy of low-dose theophylline plus ICS therapy on chronic obstructive pulmonary disease (COPD) but the results are discrepant. METHOD: We conducted searches in electronic database such as PubMed, Web Of Science, Cochrane Library, and Embase to find out original studies. Stata/SE 15.0 was used to perform all data analysis. RESULT: A total of 47,556 participants from 7 studies were included in our analysis and the sample size of each study varied from 24 to 10,816. Theophylline as an add-on therapy to ICS was not associated with the reduction of COPD exacerbations (HR: 1.08, 95% CI: 0.97 to 1.19, I2 = 95.2%). Instead, the theophylline group demonstrated a higher hospitalization rate (HR: 1.12, 95% CI: 1.10 to 1.15, I2 = 20.4%) and mortality (HR: 1.19, 95% CI: 1.14 to 1.25, I2 = 0%). Further, the anti-inflammatory effect of low-dose theophylline as an adjunct to ICS on COPD was controversial. Besides, the theophylline group showed significant improvement in lung function compared with the non-theophylline group. CONCLUSION: Based on current evidence, low-dose theophylline as add-on therapy to ICS did not reduce the exacerbation rate. Instead, the hospitalization rate and mortality increased with theophylline. Thus, we do not recommend adding low-dose theophylline to ICS therapy in COPD patients. TRIAL REGISTRATION: PROSPERO Registration CRD42021224952.

Prevalence of chronic obstructive pulmonary disease at high altitude: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Recently, several studies have investigated the prevalence of chronic obstructive pulmonary disease (COPD) at high altitude (>1,500 m). However, much remains to be understood about the correlation between altitude and COPD. We aimed to summarize the prevalence of COPD at high-altitudes and find out if altitude could be a risk factor for COPD. METHODS: We searched PubMed/Medline, Cochrane Library, Web of Science, SCOPUS, OVID, Chinese Biomedical Literature Database (CBM) and Embase databases from inception to April 30th, 2019, with no language restriction. We used STATA 14.0 to analyze the extracted data. A random-effect model was used to calculate the combined OR and 95% CI. Heterogeneity was assessed by the I 2 statistic versus P-value. We performed a subgroup analysis to analyze possible sources of heterogeneity. The Egger's test and the Begg's test were used to assess any publication bias. RESULTS: We retrieved 4,574 studies from seven databases and finally included 10 studies (54,578 participants). Males ranged from 18.8% to 49.3% and the population who smoked ranged from 3.3% to 53.3%. The overall prevalence of COPD at high-altitude was 10.0% (95% CI [0.08-0.12], P < 0.001). In a subgroup analysis, based on different regions, the results showed that the prevalence in Asia was higher than that in Europe and America. Seven studies compared the relationship between the prevalence of COPD at high-altitudes and the lowlands. The results showed that altitude was not an independent risk factor for the prevalence of COPD (ORadj = 1.18, 95% CI [0.85-1.62], P = 0.321). There was no publication bias among the studies. CONCLUSIONS: Our study found a higher prevalence of COPD at high-altitudes than those from average data. However, altitude was not found to be an independent risk factor for developing COPD (PROSPERO Identifier: CRD42019135012).