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Journal of Ethnopharmacology Jun 2024Longdan zhike tablet (LDZK) is a Tibetan medicine formula commonly used in the highland region of Tibet, China, to ameliorate respiratory diseases, such as acute...
ETHNOPHARMACOLOGICAL RELEVANCE
Longdan zhike tablet (LDZK) is a Tibetan medicine formula commonly used in the highland region of Tibet, China, to ameliorate respiratory diseases, such as acute bronchitis and asthma. In Chinese traditional medicine, some herbal formulas with anti-inflammatory properties targeting the respiratory system are clinically adopted as supplementary therapies for chronic obstructive pulmonary disease (COPD). However, the specific anti-COPD effects of LDZK remain to be evaluated.
AIM OF THE STUDY
The aim of this study is to identify the principal bioactive compounds in LDZK, and elucidate the effects and mechanisms of the LDZK on COPD.
METHODS
High-resolution mass spectrometry was utilized for a comprehensive characterization of the chemical composition of LDZK. The therapeutic effects of LDZK were assessed on the LPS-papain-induced COPD mouse model, and LPS-induced activation model of A549 cells. The safety of LDZK was evaluated by orally administering a single dose of 30 g/kg to rats and monitoring physiological and biochemical indicators after a 14-day period. Network pharmacology and Western blot analysis were employed for mechanism prediction of LDZK.
RESULTS
A comprehensive analysis identified a total of 45 compounds as the major constituents of LDZK. Oral administration of LDZK resulted in notable ameliorative effects in respiratory function, accompanied by reduced inflammatory cell counts and cytokine levels in the lungs of COPD mice. Acute toxicity tests demonstrated a favorable safety profile at a dose equivalent to 292 times the clinically prescribed dose. In vitro studies revealed that LDZK exhibited protective effects on A549 cells by mitigating LPS-induced cellular damage, reducing the release of NO, and downregulating the expression of iNOS, COX2, IL-1β, IL-6, and TNF-α. Network pharmacology and Western blot analysis indicated that LDZK primarily modulated the MAPK signaling pathway and inhibited the phosphorylation of p38/ERK/JNK.
CONCLUSIONS
LDZK exerts significant therapeutic effects on COPD through the regulation of the MAPK pathway, suggesting its potential as a promising adjunctive therapy for the treatment of chronic inflammation in COPD.
Topics: Rats; Mice; Animals; Medicine, Tibetan Traditional; Lipopolysaccharides; Pulmonary Disease, Chronic Obstructive; Lung; Signal Transduction
PubMed: 38522625
DOI: 10.1016/j.jep.2024.118082 -
Frontiers in Pharmacology 2024Acute respiratory tract infections (ARTIs) are the most common cause of morbidity and mortality worldwide, with most people experiencing at least one episode per year....
Acute respiratory tract infections (ARTIs) are the most common cause of morbidity and mortality worldwide, with most people experiencing at least one episode per year. Current treatment options are mainly symptomatic therapy. Antivirals, antibiotics, and glucocorticoids are of limited benefit for most infections. Traditional Chinese medicine has shown potential benefits in the treatment of ARTIs. The objective of this study was to determine the efficacy, effectiveness, and safety of () as monotherapy or as part of an herb mixture for ARTIs. Eight databases and two clinical trial registries were searched from inception to 8 February 2023 for randomized controlled trials (RCTs) evaluating any preparation involving without language restrictions. The Risk of Bias Tool 2.0 was used to assess the risk of bias of the included trials. RevMan 5.3 software was used for data analyses with effects estimated as risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals (CIs). The online GRADEpro tool was used to assess the certainty of the evidence, if available. Forty-two RCTs involving 6,879 patients with ARTIs were included, with all trials investigating as part of an herbal mixture. Of the included trials, the majority (38/42) were considered high risk. Compared to the placebo, preparations improved the cure rate [RR = 1.60, 95% CI (1.13, 2.26)] and fever clearance time [MD = -2.73 h, 95% CI (-4.85, -0.61)]. Compared to usual care alone, preparations also significantly improved the cure rate [RR = 1.57, 95% CI (1.36, 1.81)] and fever clearance time [SMD = -1.24, 95% CI (-2.37, -0.11)]. preparations plus usual care compared to usual care alone increased the cure rate [RR = 1.55, 95% CI (1.35, 1.78)], shortened the fever clearance time [MD = -19.31 h, 95% CI (-33.35, -5.27)], and improved FEV1 [ MD = 0.19 L, 95% CI (0.13, 0.26)] and FVC [ MD = 0.16 L, 95% CI (0.03, 0.28)]. Low- or very low-certainty evidence suggests that preparations may improve the cure rate of ARTIs, shorten the fever clearance time in febrile patients, and improve the pulmonary function of patients with acute exacerbation of chronic obstructive pulmonary disease or chronic bronchitis. However, these findings are inconclusive and need to be confirmed in rigorously designed trials. : PROSPERO, identifier CRD42021239936.
PubMed: 38510651
DOI: 10.3389/fphar.2024.1242525 -
European Journal of Pediatrics Jun 2024Acute bronchiolitis is among the most common causes of hospitalizations in infants worldwide. Associations between weight and severity of respiratory syncytial virus...
Acute bronchiolitis is among the most common causes of hospitalizations in infants worldwide. Associations between weight and severity of respiratory syncytial virus (RSV) bronchiolitis remain unclear. The aim of this study was to evaluate this association. A single-center, retrospective cohort study of infants aged under 24 months, who were hospitalized between 2018 and 2022 for RSV bronchiolitis. Data from computerized medical records were extracted using the MDclone platform. Participants were divided into three groups according to weight percentiles: underweight (below 5th percentile), normal-weight, and overweight (above 85th percentile). A total of 1936 infants (mean age 6.3 months, 55% males) were included, comprising 274 infants who were underweight, 1470 with normal weight, and 192 with overweight. Underweight infants had a higher rate of admission to the pediatric intensive care unit (PICU) (9.1% vs. 3.5%, P < 0.005) and prolonged length of stay (LOS) in the hospital (3.13 vs. 2.79 days P < 0.001) compared to those with normal weight. Hyponatremia was also more common in the underweight group (23% vs. 15%, P < 0.001). A multivariable model accounting for prematurity and birthweight predicted a relative risk of 2.01 (95% CI 1.13-3.48, P = 0.015) for PICU admission and 1.42 (95% CI 1.17-1.7, P < 0.001) for a prolonged LOS. Being overweight was not associated with a more severe disease. Conclusion: Underweight infants, hospitalized for RSV bronchiolitis, had a more severe disease course with a higher complication rate, including PICU admission and prolonged LOS. Thus, careful attention and supervision should be given to this subgroup of infants. What is Known: • Established risk factors for severe bronchiolitis include prematurity, BPD, CHD, and compromised immunity. • Abnormal weight status has been associated with an increased risk for morbidity and mortality from infectious diseases, proposedly due to the effects on endocrine and immunologic systems. What is New: • Underweight infants hospitalized with RSV bronchiolitis face an independent risk of PICU admission and prolonged hospital stay. • Conversely, overweight infants did not display associations with severity measures in our study.
Topics: Humans; Male; Infant; Retrospective Studies; Female; Respiratory Syncytial Virus Infections; Hospitalization; Bronchiolitis, Viral; Length of Stay; Body Weight; Thinness; Infant, Newborn; Risk Factors; Severity of Illness Index; Intensive Care Units, Pediatric
PubMed: 38507064
DOI: 10.1007/s00431-024-05521-7 -
Journal of Thoracic Disease Feb 2024Roflumilast is effective in reducing acute exacerbation in patients with chronic obstructive pulmonary disease (COPD) at high risk of severe exacerbation. Clinical...
BACKGROUND
Roflumilast is effective in reducing acute exacerbation in patients with chronic obstructive pulmonary disease (COPD) at high risk of severe exacerbation. Clinical traits related to the benefits of roflumilast need to be evaluated in patients with COPD.
METHODS
A longitudinal observational study in patients newly diagnosed with COPD was conducted using claims data from the Health Insurance Review and Assessment Service in South Korea from 2012-2020 after a 2-year washout period. The primary outcome was to estimate the ratio of hazard ratio (RHR) of roflumilast for moderate-to-severe exacerbation in prespecified subgroups. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) for moderate-to-severe exacerbations.
RESULTS
Among 823,862 patients with COPD, 0.6% used roflumilast. The adjusted HR of roflumilast for moderate-to-severe exacerbations was reduced when treated for ≥3 months (RHR =0.558). Interaction effects of the variables on the HR of roflumilast for moderate-to-severe exacerbation were identified. The adjusted HR of roflumilast for moderate-to-severe exacerbation was significantly reduced in several subgroups: older age (65 years > age ≥50 years, RHR =0.838; age ≥65 years, RHR =0.818), a higher Charlson comorbidity index (1, RHR =0.832; 2, RHR =0.798; ≥3, RHR =0.790), history of exacerbation (RHR =0.886), bronchiectasis (RHR =0.774), chronic bronchitis (RHR =0.793), inhaled therapy [mono-bronchodilator, RHR =0.824; inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA), RHR =0.591; LABA/long-acting muscarinic antagonist (LAMA), RHR =0.822; ICS/LABA/LAMA, RHR =0.570], methylxanthine (RHR =0.853), and statin (RHR =0.888).
CONCLUSIONS
The benefit of roflumilast in moderate-to-severe exacerbations was estimated to be greater in specific subgroups of patients with COPD. Personalised approaches to roflumilast based on clinical phenotypes would be effective for COPD.
PubMed: 38505074
DOI: 10.21037/jtd-23-1129 -
Trials Mar 2024Acute viral bronchiolitis is the most common reason for hospitalization of infants in the USA. Infants hospitalized for bronchiolitis are at high risk for recurrent...
Bronchiolitis recovery and the use of High Efficiency Particulate Air (HEPA) Filters (The BREATHE Study): study protocol for a multi-center, parallel, double-blind, randomized controlled clinical trial.
BACKGROUND
Acute viral bronchiolitis is the most common reason for hospitalization of infants in the USA. Infants hospitalized for bronchiolitis are at high risk for recurrent respiratory symptoms and wheeze in the subsequent year, and longer-term adverse respiratory outcomes such as persistent childhood asthma. There are no effective secondary prevention strategies. Multiple factors, including air pollutant exposure, contribute to risk of adverse respiratory outcomes in these infants. Improvement in indoor air quality following hospitalization for bronchiolitis may be a prevention opportunity to reduce symptom burden. Use of stand-alone high efficiency particulate air (HEPA) filtration units is a simple method to reduce particulate matter ≤ 2.5 µm in diameter (PM), a common component of household air pollution that is strongly linked to health effects.
METHODS
BREATHE is a multi-center, parallel, double-blind, randomized controlled clinical trial. Two hundred twenty-eight children < 12 months of age hospitalized for the first time with bronchiolitis will participate. Children will be randomized 1:1 to receive a 24-week home intervention with filtration units containing HEPA and carbon filters (in the child's sleep space and a common room) or to a control group with units that do not contain HEPA and carbon filters. The primary objective is to determine if use of HEPA filtration units reduces respiratory symptom burden for 24 weeks compared to use of control units. Secondary objectives are to assess the efficacy of the HEPA intervention relative to control on (1) number of unscheduled healthcare visits for respiratory complaints, (2) child quality of life, and (3) average PM levels in the home.
DISCUSSION
We propose to test the use of HEPA filtration to improve indoor air quality as a strategy to reduce post-bronchiolitis respiratory symptom burden in at-risk infants with severe bronchiolitis. If the intervention proves successful, this trial will support use of HEPA filtration for children with bronchiolitis to reduce respiratory symptom burden following hospitalization.
TRIAL REGISTRATION
NCT05615870. Registered on November 14, 2022.
Topics: Child; Infant; Humans; Quality of Life; Air Filters; Air Pollution, Indoor; Asthma; Particulate Matter; Dust; Bronchiolitis; Carbon; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38504367
DOI: 10.1186/s13063-024-08012-0 -
Journal of Virology Apr 2024Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry....
Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin-Darby bovine kidney), and NBL-6 cells (E. Derm cells). Mechanistic investigations revealed that hyperoside induces heme oxygenase-1 expression by activating the c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis, alleviating oxidative stress and triggering a downstream antiviral interferon response. Accordingly, hyperoside inhibits EHV-8 infection. Meanwhile, hyperoside can also mitigate EHV-8-induced injury in the lungs of infected mice. These results indicate that hyperoside may serve as a novel antiviral agent against EHV-8 infection.IMPORTANCEHyperoside has been reported to suppress viral infections, including herpesvirus, hepatitis B virus, infectious bronchitis virus, and severe acute respiratory syndrome coronavirus 2 infection. However, its mechanism of action against equine herpesvirus type 8 (EHV-8) is currently unknown. Here, we demonstrated that hyperoside significantly inhibits EHV-8 adsorption and internalization in susceptible cells. This process induces HO-1 expression via c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis activation, alleviating oxidative stress and triggering an antiviral interferon response. These findings indicate that hyperoside could be very effective as a drug against EHV-8.
Topics: Animals; Cattle; Mice; Rabbits; Antiviral Agents; Herpesviridae Infections; Herpesvirus 1, Equid; Horses; Interferons; JNK Mitogen-Activated Protein Kinases; Kelch-Like ECH-Associated Protein 1; MAP Kinase Signaling System; NF-E2-Related Factor 2; Oxidative Stress; Quercetin; Cell Line
PubMed: 38499512
DOI: 10.1128/jvi.00159-24 -
JMIR Public Health and Surveillance Mar 2024Live attenuated vaccines may be used to prevent nontargeted diseases such as lower respiratory tract infections (LRTIs) due to their nonspecific effects (NSEs).
Investigating Nonspecific Effects of the Live-Attenuated Japanese Encephalitis Vaccine on Lower Respiratory Tract Infections in Children Aged 25-35 Months: Retrospective Cohort Study.
BACKGROUND
Live attenuated vaccines may be used to prevent nontargeted diseases such as lower respiratory tract infections (LRTIs) due to their nonspecific effects (NSEs).
OBJECTIVE
We aimed to analyze the NSEs of the Japanese encephalitis vaccine on pediatric LRTIs in children aged 25 months to 35 months.
METHODS
A retrospective cohort study was conducted by using a population-based electronic health record database in Zhejiang, China. Enrolled participants were children born from January 1, 2017, to December 31, 2017, and who were inoculated with the live-attenuated Japanese encephalitis vaccine (JE-L) or inactivated Japanese encephalitis vaccine (JE-I) as the most recent vaccine at 24 months of age. The study was carried out between January 1, 2019, and December 31, 2019. All inpatient and outpatient hospital visits for LRTIs among children aged 25 months to 35 months were recorded. The Andersen-Gill model was used to assess the NSEs of JE-L against LRTIs in children and compared with those of JE-I as the most recent vaccine.
RESULTS
A total of 810 children born in 2017 were enrolled, of whom 585 received JE-L (JE-L cohort) and 225 received JE-I (JE-I cohort) as their last vaccine. The JE-L cohort showed a reduced risk of LRTIs (adjusted hazard ratio [aHR] 0.537, 95% CI 0.416-0.693), including pneumonia (aHR 0.501, 95% CI 0.393-0.638) and acute bronchitis (aHR 0.525, 95% CI 0.396-0.698) at 25 months to 35 months of age. The NSEs provided by JE-L were especially pronounced in female children (aHR 0.305, 95% CI 0.198-0.469) and children without chronic diseases (aHR 0.553, 95% CI 0.420-0.729), without siblings (aHR 0.361, 95% CI 0.255-0.511), with more than 30 inpatient and outpatient hospital visits prior to 24 months of age (aHR 0.163, 95% CI 0.091-0.290), or with 5 to 10 inpatient and outpatient hospital visits due to infectious diseases prior to 24 months old (aHR 0.058, 95% CI 0.017-0.202).
CONCLUSIONS
Compared with JE-I, receiving JE-L as the most recent vaccine was associated with lower risk of inpatient and outpatient hospital visits for LRTIs among children aged 25 months to 35 months. The nature of NSEs induced by JE-L should be considered for policymakers and physicians when recommending JE vaccines to those at high risk of infection from the Japanese encephalitis virus.
Topics: Humans; Female; Child; Child, Preschool; Japanese Encephalitis Vaccines; Retrospective Studies; Vaccines; Respiratory Tract Infections; China
PubMed: 38498052
DOI: 10.2196/53040 -
Open Forum Infectious Diseases Mar 2024Community-acquired pneumonia is a well-studied condition; yet, in the urgent care setting, patient characteristics and adherence to guideline-recommended care are poorly...
BACKGROUND
Community-acquired pneumonia is a well-studied condition; yet, in the urgent care setting, patient characteristics and adherence to guideline-recommended care are poorly described. Within Intermountain Health, a nonprofit integrated US health care system based in Utah, more patients present to urgent care clinics (UCCs) than emergency departments (EDs) for pneumonia care.
METHODS
We performed a retrospective cohort study 1 January 2019 through 31 December 2020 in 28 UCCs within Utah. We extracted electronic health record data for patients aged ≥12 years with pneumonia diagnoses entered by the bedside clinician, excluding patients with preceding pneumonia within 30 days or missing vital signs. We compared UCC patients with radiographic pneumonia (n = 4689), without radiographic pneumonia (n = 1053), without chest imaging (n = 1472), and matched controls with acute cough/bronchitis (n = 15 972). Additional outcomes were 30-day mortality and the proportion of patients with ED visits or hospital admission within 7 days after the index encounter.
RESULTS
UCC patients diagnosed with pneumonia and possible/likely radiographic pneumonia by radiologist report had a mean age of 40 years and 52% were female. Almost all patients with pneumonia (93%) were treated with antibiotics, including those without radiographic confirmation. Hospital admissions and ED visits within 7 days were more common in patients with radiographic pneumonia vs patients with "unlikely" radiographs (6% vs 2% and 10% vs 6%, respectively). Observed 30-day all-cause mortality was low (0.26%). Patients diagnosed without chest imaging presented similarly to matched patients with cough/acute bronchitis. Most patients admitted to the hospital the same day after the UCC visit (84%) had an interim ED encounter. Pneumonia severity scores (pneumonia severity index, electronic CURB-65, and shock index) overestimated patient need for hospitalization.
CONCLUSIONS
Most UCC patients with pneumonia were successfully treated as outpatients. Opportunities to improve care include clinical decision support for diagnosing pneumonia with radiographic confirmation and development of pneumonia severity scores tailored to the UCC.
PubMed: 38456194
DOI: 10.1093/ofid/ofae096 -
Journal of Cardiac Failure Mar 2024Fontan physiology leads to chronic changes in other organ systems that may affect long-term survival and the success of heart transplantation. Inadequate assessment and...
BACKGROUND
Fontan physiology leads to chronic changes in other organ systems that may affect long-term survival and the success of heart transplantation. Inadequate assessment and treatment of the extra-cardiac effects of Fontan may contribute to poor outcomes. Severity-graded/ordinal consensus definitions of Fontan complications are lacking, which limits understanding of how Fontan-specific morbidity affects patients' outcomes.
METHODS AND RESULTS
A panel of Fontan patient and physiology experts, including pediatric, adult congenital, heart failure, and critical-care cardiology as well as pediatric nephrology, hepatology and psychology, convened to develop definitions of Fontan complications. Definitions were created by using a severity-graded ordinal scale: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, disabling or life threatening. Following definition creation, a second panel of 21 experts in Fontan circulatory failure used a modified Delphi methodology to modify and vote on definitions until consensus (> 90% agreement without recommended further modification) was reached on final definitions. After 3 rounds of modifications and voting, consensus agreement was achieved on all Fontan-specific definitions. The defined complications and morbidities of Fontan include: anatomic Fontan pathway obstruction, cyanosis, systemic venous abnormalities resulting from venous insufficiency, atrial arrhythmia, ventricular arrhythmia, bradycardia, chronic pleural effusions, chronic ascites, protein-losing enteropathy, plastic bronchitis, hemoptysis and pulmonary hemorrhage, sleep apnea, Fontan-associated liver disease, portal and hepatic variceal disease, acute kidney injury affecting clinical treatment, polycythemia, thrombotic disease, recurrent or severe bacterial infection, skin atrophy, adrenal insufficiency, physical impact of previous stroke, mood/behavior disorder, and neurodevelopmental disorder.
CONCLUSION
Consensus and severity-graded definitions of Fontan-specific cardiac and extra-cardiac complications were achieved and are available for use in research. They will allow future robust analyses of Fontan patient outcomes.
PubMed: 38452996
DOI: 10.1016/j.cardfail.2024.02.015