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1.
Drug Des Devel Ther ; 18: 1865-1874, 2024.
Article En | MEDLINE | ID: mdl-38828019

Purpose: This study was designed to investigate the effects of preadministration of nalmefene before general anesthesia induction on sufentanil-induced cough (SIC) in patients undergoing breast surgery. Patients and Methods: A total of 105 patients scheduled for elective breast surgery under general anesthesia were selected and randomly assigned into three groups: normal saline (Group C), low-dose nalmefene 0.1 µg·kg-1 (Group LN), and high-dose nalmefene 0.25 µg·kg-1 (Group HN). Sufentanil 0.5 µg·kg-1 was injected intravenously within 2 s after 5 min of intervention. The count and severity of cough within 2 min after sufentanil injection, as well as the time to first cough, were recorded. In addition, we also collected intraoperative hemodynamic data, postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 24 h after surgery. Results: Compared to Group C, the incidence of SIC was significantly lower in Group LN and HN (64.7% vs 30.3% and 14.7%, respectively; P < 0.001), but no significant difference was observed between the two groups (P=0.126). Compared to Group C, the risk factors decreased by 53.4% (95% confidence interval [CI] =0.181-0.735, P=0.008) in Group LN and by 75.9% (95% CI=0.432-0.898, P=0.001) in Group HN. Of the patients with SIC, less frequent SIC within 2 min after induction and a lower proportion of severe coughs were observed than Group C (P < 0.05), and no difference was detected between Group LN and HN. Additionally, the onset time to the first SIC did not differ significantly between the groups. Intraoperative hemodynamic data, postoperative pain scores, and side effects in the first 24 h did not differ among the groups. Conclusion: Preadministration of nalmefene prior to induction of general anesthesia effectively suppressed SIC in patients undergoing breast surgery, without affecting intraoperative hemodynamic fluctuation and postoperative pain intensity.


Anesthesia, General , Cough , Naltrexone , Sufentanil , Humans , Sufentanil/administration & dosage , Sufentanil/adverse effects , Anesthesia, General/adverse effects , Cough/drug therapy , Cough/chemically induced , Female , Naltrexone/analogs & derivatives , Naltrexone/administration & dosage , Naltrexone/pharmacology , Double-Blind Method , Middle Aged , Adult , Breast/surgery , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Dose-Response Relationship, Drug
2.
NPJ Prim Care Respir Med ; 34(1): 9, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724543

This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses' use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15-0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29-1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17-1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in ß-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption.


Anti-Bacterial Agents , C-Reactive Protein , Cough , Humans , Anti-Bacterial Agents/therapeutic use , C-Reactive Protein/metabolism , C-Reactive Protein/analysis , Male , Female , Middle Aged , Cough/drug therapy , Adult , Communication , Acute Disease , Respiratory Tract Infections/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Aged , Primary Health Care/methods , COVID-19/complications , Spain , Point-of-Care Testing
3.
Lung ; 202(3): 275-280, 2024 Jun.
Article En | MEDLINE | ID: mdl-38733542

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.


Cough , Nitric Oxide , Humans , Cough/drug therapy , Female , Middle Aged , Male , Prospective Studies , Administration, Inhalation , Chronic Disease , Nitric Oxide/metabolism , Nitric Oxide/analysis , Aged , Treatment Outcome , Fractional Exhaled Nitric Oxide Testing , Androstadienes/administration & dosage , Adult , Severity of Illness Index , Surveys and Questionnaires , Exhalation , Adrenal Cortex Hormones/administration & dosage , Chronic Cough
4.
Sci Rep ; 14(1): 11956, 2024 05 25.
Article En | MEDLINE | ID: mdl-38796481

The Montreal consensus recognizes chronic cough as an extra-esophageal manifestation of gastroesophageal reflux disease. We performed a meta-analysis to assess the effects of acid-suppressive medications in adults with non-specific chronic cough. The protocol was registered on PROSPERO (CRD42022368769). Placebo-controlled randomized trials evaluating the impact of acid-suppressive medications on persistent cough were included. The systematic search was performed on the 1st of November 2022 in three databases. A random-effects model was used for the calculations. The effect size was the standardized mean difference (SMD) with 95% confidence interval (CI). A total number of 11 double-blinded placebo-controlled randomized trials were included in the meta-analysis. Data showed that compared to placebo, PPIs decreased the severity of cough (SMD 0.33; CI 0.05; 0.61). Therapeutic response was not different in patients with non-specific chronic cough only, compared to those with laryngopharyngeal reflux. Prolonged treatment durations did not result in greater symptomatic improvement, with SMD 0.33 (CI - 0.22; 0.88), 0.31 (CI - 1.74; 2.35), 0.32 (CI - 0.29; 0.93) and 0.34 (CI - 0.16; 0.85), following 4, 6, 8 and 12 weeks of treatment, respectively. The pooled analysis of the improvement in quality of life with PPIs found an SMD of 0.39 (CI - 0.51; 1.29). PPIs mildly decrease the severity of non-specific chronic cough, irrespective of treatment duration.


Cough , Proton Pump Inhibitors , Proton Pump Inhibitors/therapeutic use , Cough/drug therapy , Humans , Chronic Disease , Gastroesophageal Reflux/drug therapy , Randomized Controlled Trials as Topic , Severity of Illness Index , Treatment Outcome , Chronic Cough
5.
Sci Rep ; 14(1): 11386, 2024 05 18.
Article En | MEDLINE | ID: mdl-38762573

Aspiration pneumonia is the leading cause of death in patients with Parkinson's disease. The incidence of silent aspiration is high in such patients owing to decreased pharyngeal and laryngeal sensation; thus, interventions for this condition may help prevent pneumonia. In this single-arm, open-label study, we used a cervical percutaneous interferential current stimulation device to activate pharyngeal and laryngeal sensory nerves. We evaluated its effectiveness in patients with Hoehn-Yahr stages 2-4 Parkinson's disease. The primary endpoint was the proportion of patients with a normal cough reflex after consuming 1% citric acid at the end of the intervention compared with baseline measurements. In total, 25 patients received neck percutaneous interferential current stimulation for 20 min twice weekly for 8 weeks. Afterward, the proportion of patients with a normal cough reflex after 1% citric acid consumption increased significantly (p = 0.001), whereas other indicators, such as tongue pressure, peak expiratory flow, and penetration or aspiration during videofluoroscopic examination, remained unchanged. A longer duration of illness, higher Unified Parkinson's Disease Rating Scale total scores, and higher levodopa equivalent daily doses were significantly associated with improved cough test outcomes. Hence, cervical percutaneous interferential current stimulation significantly improved cough reflexes and may improve silent aspiration. Trial Registration: Japan Registry of Clinical Trials, jRCTs062220013, first registered 09/05/2022.


Citric Acid , Cough , Parkinson Disease , Humans , Parkinson Disease/therapy , Parkinson Disease/physiopathology , Female , Male , Aged , Cough/drug therapy , Middle Aged , Pneumonia, Aspiration/etiology , Pneumonia, Aspiration/prevention & control , Electric Stimulation Therapy/methods
6.
BMC Public Health ; 24(1): 1089, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38641808

INTRODUCTION: Fever and cough in under-five children are common and predominately self-limiting illnesses. Inappropriate prescribing of antibiotics in sub-Saharan Africa is a significant public health concern. However, prescription sources and use among children with fever or cough have not been explored. Therefore, we explored the factors associated with the use of antibiotics obtained from prescription and non-prescription sources for children with illnesses associated with fever and cough. METHODS: A secondary data analysis was conducted based on the Demographic and Health Survey (DHS) data from 37 sub-Saharan African countries. A total weighted sample of 18,866 under-five children who had a fever/cough and took antibiotics were considered for this study. Given the hierarchical nature of DHS data and the use of antibiotics prescribed from the formal healthcare setting (> 10%), a multilevel modified poisson regression model was fitted. Deviance was used for model comparison and the model with the lowest deviance value was chosen as the best-fitted model. Variables with p ≤ 0.2 in the bivariable analysis were considered for the multivariable modified poisson regression model. In the multivariable multilevel modified poisson regression model, the Adjusted Prevalence Odds Ratio (APOR) with a 95% Confidence Interval (CI) and p-value < 0.05 were reported to declare a significant association with taking antibiotics for fever/cough prescribed from formal healthcare setting. RESULTS: In sub-Saharan Africa, the proportion of use of antibiotics from informal healthcare setting for fever and cough among under-five children was 67.19% (95% CI: 66.51%, 67.85%). In the multilevel modified poisson regression analysis; residing in a rural area (APOR = 1.08, 95% CI: 1.04, 1.12), a child aged 36-47 months (APOR = 0.94, 95% CI: 0.90, 0.98), a child aged 48-59 months (APOR = 0.89, 95% CI: 0.84, 0.94), maternal primary education (APOR = 0.96, 95% CI: 0.93, 0.99), maternal secondary education (APOR = 0.95, 95% CI: 0.92, 0.99), belonged the middle household wealth status (APOR = 1.07, 95% CI: 1.02, 1.11), maternal exposure to news/electronic media (APR = 1.06, 95% CI: 1.02, 1.10), being from a household with 2 under-five children (APR = 0.94, 95% CI: 0.91, 0.97), being from a household with 3 under-five children (APR = 0.89, 95% CI: 0.85, 0.93), being from a household with 4 under-five children (APR = 0.90, 95% CI: 0.83, 0.98), and children of caregivers who were not involved in decision-making for their child health issues were significantly associated with taking antibiotics prescribed from formal healthcare setting for fever/cough among under-five children. CONCLUSION: Only two-thirds of the antibiotics used for children under five who had fever and cough were prescribed from formal healthcare setting. Our findings underscore the significance of addressing healthcare disparities, improving access to qualified healthcare providers, promoting maternal education, and empowering mothers in healthcare decision-making to ensure appropriate antibiotic use in this vulnerable population. Further research and interventions targeted at these factors are warranted to optimize antibiotic prescribing practices and promote responsible antibiotic use in the management of fever and cough in under-five children.


Anti-Bacterial Agents , Fever , Child , Female , Humans , Cross-Sectional Studies , Fever/drug therapy , Fever/epidemiology , Anti-Bacterial Agents/therapeutic use , Black People , Cough/drug therapy
7.
BMC Anesthesiol ; 24(1): 149, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38641778

BACKGROUND: Opioids such as sufentanil are used as anaesthetics due to their rapid action and superior analgesic effect. However, sufentanil induces a huge cough in paediatric patients. In contrast, intravenous (IV) lidocaine suppresses opioid-induced cough in children, but its use is limited due to anaesthetists' concern about its toxicity. Therefore, this study aimed to evaluate the effect of dose-dependent IV lidocaine on sufentanil-induced cough (SIC) in paediatric patients. METHODS: A total of 188 patients aged 3-12 years scheduled for elective tonsillectomy with or without adenoidectomy were enrolled and divided into four groups depending on different dose of lidocaine: A (0 mg.kg-1), B (1 mg.kg-1), C (1.5 mg.kg-1), and D (2 mg.kg-1). The primary outcome was the SIC grade observed during the induction of general anaesthesia. The secondary outcomes were the incidence of SIC, mean arterial pressure, and heart rate at T0, T1, T2, T3, T4, and T5. RESULTS: The SIC grade was significantly different between groups A and D (P = 0.04) and between groups B and D (P = 0.03). Moreover, the incidence of SIC in groups A, B, C, and D was 81%, 87%, 68%, and 64%, respectively, and the difference between groups B and C (P = 0.03) and between groups B and D (P = 0.0083) was statistically significant. No statistical differences were observed in the hemodynamic parameters between the groups. The incidence of severe cough was statistically different between group D and group A (P < 0.0001), between group D and group B (P < 0.0001), and between group D and group C (P < 0.0001) respectively. CONCLUSIONS: Lidocaine suppresses SIC in a dose-dependent manner without severe adverse events. IV lidocaine can be used in paediatric patients safely and efficiently, and the median effective dose was 1.75 mg/kg. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of Yichang Central People's Hospital (HEC-KYJJ-2020-038-02), The trial was registered at www.chictr.org.cn (ChiCTR2100053006).


Lidocaine , Sufentanil , Humans , Child , Sufentanil/adverse effects , Lidocaine/adverse effects , Analgesics, Opioid , Anesthetics, Intravenous/adverse effects , Cough/chemically induced , Cough/prevention & control , Cough/drug therapy
8.
AMA J Ethics ; 26(4): E289-294, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38564743

This commentary responds to a case about diethylene glycol-contaminated glycerin in cough syrup. Glycerin is a commonly used excipient in medicines to improve texture and taste. Excipients are typically pharmacologically inactive ingredients contained in prescription and over-the-counter drugs that play a critical role in the delivery, effectiveness, and stability of active drug substances. The commentary first canvasses how contaminants enter the excipient supply chains. One way is by misleading labeling or intentional adulteration by manufacturers or suppliers. Another way is by human or systemic error. This commentary then discusses quality control testing and suggests the ethical and clinical importance of increased transparency in excipient supply chains.


Excipients , Glycerol , Child , Humans , Excipients/adverse effects , Pharmaceutical Preparations , Drug Contamination , Cough/drug therapy
9.
Regul Toxicol Pharmacol ; 149: 105621, 2024 May.
Article En | MEDLINE | ID: mdl-38608922

Although the United States Food & Drug Administration (FDA) has provided guidance on the control of drug degradants for prescription drugs, there is less guidance on how to set degradant specifications for FDA OTC monograph drugs. Given that extensive impurity testing was not part of the safety paradigm in original OTC monographs, a weight of evidence (WOE) approach to qualify OTC degradants is proposed. This approach relies on in silico tools and read-across approaches alongside standard toxicity testing to determine safety. Using several drugs marketed under 21 CFR 341 as case studies, this research demonstrates the utility of a WOE approach across data-rich and data-poor degradants. Based on degradant levels ranging from 1 to 4% of the maximum daily doses of each case study drug and 10th percentile body weight data for each patient group, children were recognized as having the highest potential exposure relative to adults per body mass. Depending on data availability and relationship to the parent API, margins of safety (MOS) or exposure margins were calculated for each degradant. The findings supported safe use, and indicated that this contemporary WOE approach could be utilized to assess OTC degradants. This approach is valuable to establish specifications for degradants in OTCs.


Antitussive Agents , Nonprescription Drugs , United States Food and Drug Administration , Nonprescription Drugs/adverse effects , Humans , United States , Antitussive Agents/adverse effects , Cough/drug therapy , Risk Assessment , Child , Drug Contamination , Adult , Toxicity Tests/methods , Common Cold/drug therapy
10.
J Tradit Chin Med ; 44(2): 396-402, 2024 Apr.
Article En | MEDLINE | ID: mdl-38504546

OBJECTIVE: To formulate the first clinical practice guideline for the treatment of cough using Chinese medicine based on the grading of recommendations assessment, development, and evaluation (GRADE) systematic approach, including clinical evidence, evaluation of ancient literature, and expert consensus. METHODS: In the process of development, the regulation of "evidence-based, consensus-assisted, and empirical" was followed, and a comprehensive systematic approach of recommendation assessment, GRADE, evidence-based evaluation, expert consensus, and the Delphi method was used. In the process of guideline development, evidence-based evaluation of ancient literature was included for the first time, and clinical evidence was fully integrated with clinical expert consensus. RESULTS: The clinical practice guidelines for the treatment of cough with Chinese herbal medicine were developed after a comprehensive consideration of evidence-based evaluation and expert opinions. The guideline recommendations focused on recommending herbal compound decoctions and Chinese patent medicines for cough in different conditions. Based on the GRADE systematic approach, we conducted an evidence-based evaluation of the recommended Chinese patent medicines one by one; meanwhile, the expert consensus method was used to unify the recommendations of both. CONCLUSION: Based on clinical evidence, ancient literature evaluation, and expert consensus, a clinical practice guideline for Traditional Chinese Medicine (TCM) in the treatment of cough was developed, providing the first current clinical practice guideline for domestic and foreign TCM and Western medicine practitioners, especially respiratory professionals at home and abroad.


Drugs, Chinese Herbal , Medicine, Chinese Traditional , Humans , Drugs, Chinese Herbal/therapeutic use , Reference Standards , Nonprescription Drugs , Cough/drug therapy
12.
Pediatr Pulmonol ; 59(6): 1541-1551, 2024 Jun.
Article En | MEDLINE | ID: mdl-38501316

This meta-analysis aims to assess the clinical effectiveness of combination therapy with montelukast sodium for the treatment of cough variant asthma (CVA) in children, intending to provide clinical evidence and data to guide the selection of clinical therapy. A literature review was conducted using numerous databases, including China National Knowledge Infrastructure (CNKI), Wanfang database, Embase, PubMed, and Web of Science, from inception to December 2023. Trials meeting the criteria for the combined treatment of montelukast sodium for CVA in children were included. Stata 16.0 software was utilized for meta-analysis. The combined treatment group received montelukast sodium in addition to the control group, while the control group received budesonide, fluticasone propionate, salmeterol-fluticasone, or ketotifen alone. This investigation included 18 papers. All subjects were from the Chinese population. Compared to the control group, the combined treatment group demonstrated a higher effective rate (relative ratio [RR] = 1.23, 95% confidence interval [CI]: 1.18-1.29, p < .001), but no difference in the incidence of adverse reactions (RR = 0.65, 95% CI: 0.42-1.02, p = .060) after treatment. Moreover, the peak expiratory flow (PEF) (SMD = 1.69, 95% CI: 1.09-2.30, p < .001), forced vital capacity (FVC) (SMD = 1.67, 95% CI: 0.94-2.39, p < .001), forced expiratory volume in 1 s (FEV1) (SMD = 1.74, 95% CI: 1.09-2.40, p < .001), and FEV1/FVC (SMD = 1.84, 95% CI: 0.41-3.28, p = .012) were significantly higher in the combined treatment group than in the control group after treatment. Compared with the control group, the levels of tumor necrosis factor-α (SMD = -2.38, 95% CI: -3.22 to -1.55, p < .001), IL-4 (SMD = -2.65, 95% CI: -3.26 to -2.04, p < .001), and IgE (SMD = -2.98, 95% CI: -3.24 to -2.72, p < .001) were significantly lower in the combined treatment group after treatment. The combined use of montelukast sodium in the treatment of pediatric CVA in China is associated with a significant clinical effect, making it a reasonable therapeutic approach.


Acetates , Anti-Asthmatic Agents , Asthma , Cough , Cyclopropanes , Drug Therapy, Combination , Quinolines , Sulfides , Humans , Asthma/drug therapy , Acetates/therapeutic use , Acetates/administration & dosage , Child , Cough/drug therapy , Quinolines/therapeutic use , Quinolines/administration & dosage , Cyclopropanes/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Anti-Asthmatic Agents/administration & dosage , Treatment Outcome , Cough-Variant Asthma
13.
Lung ; 202(2): 97-106, 2024 Apr.
Article En | MEDLINE | ID: mdl-38411774

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.


Antitussive Agents , Codeine , Humans , Codeine/therapeutic use , Antitussive Agents/therapeutic use , Prospective Studies , Chronic Cough , Cohort Studies , Cough/drug therapy , Cough/etiology
15.
Lancet Respir Med ; 12(4): 273-280, 2024 Apr.
Article En | MEDLINE | ID: mdl-38237620

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis. METHODS: The PACIFY COUGH study is a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial done in three specialist centres in the UK. Eligible patients aged 40-90 years had a diagnosis of idiopathic pulmonary fibrosis within 5 years, self-reported cough (lasting >8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher. Patients were randomly assigned (1:1) to placebo twice daily or controlled-release morphine 5 mg orally twice daily for 14 days followed by crossover after a 7-day washout period. Patients were randomised sequentially to a sequence group defining the order in which morphine and placebo were to be given, according to a computer-generated schedule. Patients, investigators, study nurses, and pharmacy personnel were masked to treatment allocation. The primary endpoint was percentage change in objective awake cough frequency (coughs per h) from baseline as assessed by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. Safety data were summarised for all patients who took at least one study drug and did not withdraw consent. This study was registered at ClinicalTrials.gov, NCT04429516, and has been completed. FINDINGS: Between Dec 17, 2020, and March 21, 2023, 47 participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment. Mean age was 71 (SD 7·4) years, and 31 (70%) of 44 participants were male and 13 (30%) were female. Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L (SD 0·76), mean predicted FVC was 82% (17·3), and mean predicted diffusion capacity of carbon monoxide was 48% (10·9). Of the 44 patients who were randomised, 43 completed morphine treatment and 41 completed placebo treatment. In the intention-to-treat analysis, morphine reduced objective awake cough frequency by 39·4% (95% CI -54·4 to -19·4; p=0·0005) compared with placebo. Mean daytime cough frequency reduced from 21·6 (SE 1·2) coughs per h at baseline to 12·8 (1·2) coughs per h with morphine, whereas cough rates did not change with placebo (21·5 [SE 1·2] coughs per h to 20·6 [1·2] coughs per h). Overall treatment adherence was 98% in the morphine group and 98% in the placebo group. Adverse events were observed in 17 (40%) of 43 participants in the morphine group and six (14%) of 42 patients in the placebo group. The main side-effects of morphine were nausea (six [14%] of 43 participants) and constipation (nine [21%] of 43). One serious adverse event (death) occurred in the placebo group. INTERPRETATION: In patients with cough related to idiopathic pulmonary fibrosis, low dose controlled-release morphine significantly reduced objective cough counts over 14 days compared with placebo. Morphine shows promise as an effective treatment to palliate cough in patients with idiopathic pulmonary fibrosis, and longer term studies should be the focus of future research. FUNDING: The Jon Moulton Charity Trust.


Idiopathic Pulmonary Fibrosis , Aged , Female , Humans , Male , Cough/drug therapy , Cough/etiology , Cross-Over Studies , Delayed-Action Preparations , Double-Blind Method , Idiopathic Pulmonary Fibrosis/complications , Idiopathic Pulmonary Fibrosis/drug therapy , Morphine Derivatives/therapeutic use , Prospective Studies , Treatment Outcome , Middle Aged
17.
J Ethnopharmacol ; 324: 117741, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38224794

ETHNOPHARMACOLOGICAL RELEVANCE: Zhisou Powder (ZSP), a traditional Chinese medicine (TCM) prescription, has been widely used in the clinic for the treatment of post-infectious cough (PIC). However, the exact mechanism is not clear. AIM OF THE STUDY: The aim of this study was to investigate the ameliorative effect of ZSP on PIC in mice. The possible mechanisms of action were screened based on network pharmacology, and the potential mechanisms were explored through molecular docking and in vivo experimental validation. MATERIALS AND METHODS: Lipopolysaccharide (LPS) (80µg/50 µL) was used to induce PIC in mice, followed by daily exposure to cigarette smoke (CS) for 30 min for 30 d to establish PIC model. The effects of ZSP on PIC mice were observed by detecting the number of coughs and cough latency, peripheral blood and bronchoalveolar lavage fluid (BALF) inflammatory cell counts, enzyme-linked immunosorbent assay (ELISA), and histological analysis. The core targets and key pathways of ZSP on PIC were analyzed using network pharmacology, and TRPA1 and TRPV1 were validated using RT-qPCR and western blotting assays. RESULTS: ZSP effectively reduced the number of coughs and prolonged the cough latency in PIC mice. Airway inflammation was alleviated by reducing the expression levels of the inflammatory mediators TNF-α and IL-1ß. ZSP modulated the expression of Substance P, Calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) in BALF. Based on the results of network pharmacology, the mechanism of action of ZSP may exert anti-neurogenic airway-derived inflammation by regulating the expression of TRPA1 and TRPV1 through the natural active ingredients α-spinastero, shionone and didehydrotuberostemonine. CONCLUSION: ZSP exerts anti-airway inflammatory effects through inhibition of TRPA1/TRPV1 channels regulating neuropeptides to alleviate cough hypersensitivity and has a favorable therapeutic effect on PIC model mice. It provides theoretical evidence for the clinical application of ZSP.


Lipopolysaccharides , TRPV Cation Channels , Mice , Animals , TRPA1 Cation Channel/metabolism , Lipopolysaccharides/toxicity , Powders/therapeutic use , Molecular Docking Simulation , TRPV Cation Channels/metabolism , Cough/chemically induced , Cough/drug therapy , Cough/metabolism , Inflammation/pathology , Anti-Inflammatory Agents/adverse effects
18.
Br J Gen Pract ; 74(743): e401-e407, 2024 Jun.
Article En | MEDLINE | ID: mdl-38296358

BACKGROUND: Childhood respiratory tract infections (RTIs) are common and can lead to unnecessary antibiotic use and antimicrobial resistance. The CHIldren with COugh (CHICO) intervention incorporates a clinician-focused algorithm (STARWAVe) to predict future hospitalisation risk, elicitation of carer concerns, and a carer-focused personalised leaflet recording treatment decisions and safety-netting information. AIM: To examine the implementation of the CHICO intervention by primary care clinicians. DESIGN AND SETTING: A qualitative study with primary care clinicians in England taking part in the CHICO randomised controlled trial. METHOD: Interviews explored the CHICO intervention's acceptability and use. Clinicians from a range of practices with high and low antibiotic dispensing rates were recruited. Normalisation process theory underpinned data collection and thematic analysis. RESULTS: Most clinicians liked the intervention because it was quick and easy to use, it helped elicit carer concerns, and reassured clinicians and carers of the appropriateness of treatment decisions. However, clinicians used it as a supportive aid for treatment decisions rather than as a tool for behaviour change. The accompanying advice leaflet helped explain treatment decisions and support self-care. The intervention did not always align with clinicians' usual processes, which could affect use. Increased familiarisation with the algorithm led to reduced intervention use, which was further reduced during the COVID-19 pandemic as a result of changes to practice and remote consultations. CONCLUSION: Clinicians found the CHICO intervention useful to support decision making around antibiotic prescribing and it helped discussions with carers about concerns and treatment decisions. The intervention may need to be adapted to align more with clinicians' consultation flow and remote consultations.


Anti-Bacterial Agents , Cough , Primary Health Care , Qualitative Research , Respiratory Tract Infections , Humans , Anti-Bacterial Agents/therapeutic use , Cough/drug therapy , Child , Respiratory Tract Infections/drug therapy , England , Practice Patterns, Physicians' , Algorithms , Female , Male , COVID-19
19.
Allergol. immunopatol ; 52(1): 9-15, 01 jan. 2024. tab, ilus
Article En | IBECS | ID: ibc-229171

Background: Asthma is one of the most common chronic respiratory diseases with inflammatory involvement and has a high burden worldwide. This study aimed to determine the effect of Thymus vulgaris (TV) on cough in children between 5 and 12 years old with mild to moderate asthma exacerbation. Methods: In this randomized, triple-blind clinical trial, 60 children between the ages of 5 and 12 with asthma exacerbations were randomly divided into two groups. The intervention group (n = 30) was given TV powder at a dose of 20 mg/kg every 8 hours, prepared as syrup, along with routine medical treatment for a week, and the control group (n = 30) received only routine medical treatment with placebo syrup. At the end of the week, clinical and laboratory symptoms, and spirometry data were re-recorded for both groups. Finally, the recorded factors were compared and statistically analyzed. Results: The results showed that after the intervention, activity-induced cough reduced, and difference was statistically significant between the two groups (p = 0.042), but the reduction in wheezing and breathlessness had no statistically significant difference. Spirometry data showed a significant difference in forced expiratory volume in 1 second (FEV1) between the two groups after intervention (p = 0.048), but this difference was not significant in FEV1/FVC (forced vital capacity), peak expiratory flow (PEF), and forced expiratory flow at 25–75% of the vital capacity (FEF25–75%). Conclusion: The results show that TV syrup may be useful as an adjuvant treatment in children with asthma exacerbations (AU)


Humans , Male , Female , Child, Preschool , Child , Asthma/drug therapy , Thymus Plant , Symptom Flare Up , Plant Extracts/therapeutic use , Adjuvants, Immunologic , Cough/drug therapy , Dyspnea , Treatment Outcome
20.
Allergol Immunopathol (Madr) ; 52(1): 9-15, 2024.
Article En | MEDLINE | ID: mdl-38186189

BACKGROUND: Asthma is one of the most common chronic respiratory diseases with inflammatory involvement and has a high burden worldwide. This study aimed to determine the effect of Thymus vulgaris (TV) on cough in children between 5 and 12 years old with mild to moderate asthma exacerbation. METHODS: In this randomized, triple-blind clinical trial, 60 children between the ages of 5 and 12 with asthma exacerbations were randomly divided into two groups. The intervention group (n = 30) was given TV powder at a dose of 20 mg/kg every 8 hours, prepared as syrup, along with routine medical treatment for a week, and the control group (n = 30) received only routine medical treatment with placebo syrup. At the end of the week, clinical and laboratory symptoms, and spirometry data were re-recorded for both groups. Finally, the recorded factors were compared and statistically analyzed. RESULTS: The results showed that after the intervention, activity-induced cough reduced, and difference was statistically significant between the two groups (p = 0.042), but the reduction in wheezing and breathlessness had no statistically significant difference. Spirometry data showed a significant difference in forced expiratory volume in 1 second (FEV1) between the two groups after intervention (p = 0.048), but this difference was not significant in FEV1/FVC (forced vital capacity), peak expiratory flow (PEF), and forced expiratory flow at 25-75% of the vital capacity (FEF25-75%). CONCLUSION: The results show that TV syrup may be useful as an adjuvant treatment in children with asthma exacerbations.


Asthma , Thymus Plant , Child , Humans , Child, Preschool , Asthma/drug therapy , Cough/drug therapy , Dyspnea , Adjuvants, Immunologic
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