50% efficacy dose of intravenous lidocaine in supressing sufentanil-induced cough in children: a randomised controlled trial.

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).

Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial.

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.

The traditional utilization, biological activity and chemical composition of edible fern species.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferns form an important part of the human diet. Young fern fiddleheads are mostly consumed as vegetables, while the rhizomes are often extracted for starch. These edible ferns are also often employed in traditional medicine, where all parts of the plant are used, mostly to prepare extracts. These extracts are applied either externally as lotions and baths or internally as potions, decoctions and teas. Ailments traditionally treated with ferns include coughs, colds, fevers, pain, burns and wounds, asthma, rheumatism, diarrhoea, or skin diseases (eczema, rashes, itching, leprosy). AIM OF THE REVIEW: This review aims to compile the worldwide knowledge on the traditional medicinal uses of edible fern species correlating to reported biological activities and isolated bioactive compounds. MATERIALS AND METHODS: The articles and books published on edible fern species were searched through the online databases Web of Science, Pubmed and Google Scholar, with critical evaluation of the hits. The time period up to the end of 2022 was included. RESULTS: First, the edible fern species were identified based on the literature data. A total of 90 fern species were identified that are eaten around the world and are also used in traditional medicine. Ailments treated are often associated with inflammation or bacterial infection. However, only the most common and well-known fern species, were investigated for their biological activity. The most studied species are Blechnum orientale L., Cibotium barometz (L.) J. Sm., Diplazium esculentum (Retz.) Sw., Marsilea minuta L., Osmunda japonica Thunb., Polypodium vulgare L., and Stenochlaena palustris (Burm.) Bedd. Most of the fern extracts have been studied for their antioxidant, anti-inflammatory and antimicrobial activities. Not surprisingly, antioxidant capacity has been the most studied, with results reported for 28 edible fern species. Ferns have been found to be very rich sources of flavonoids, polyphenols, polyunsaturated fatty acids, carotenoids, terpenoids and steroids and most of these compounds are remarkable free radical scavengers responsible for the outstanding antioxidant capacity of fern extracts. As far as clinical trials are concerned, extracts from only three edible fern species have been evaluated. CONCLUSIONS: The extracts of edible fern species exert antioxidant anti-inflammatory and related biological activities, which is consistent with their traditional medicinal use in the treatment of wounds, burns, colds, coughs, skin diseases and intestinal diseases. However, studies to prove pharmacological activities are scarce, and require chemical-biological standardization. Furthermore, correct botanical classification needs to be included in publications to simplify data acquisition. Finally, more in-depth phytochemical studies, allowing the linking of traditional use to pharmacological relevance are needed to be done in a standardized way.

Zhisou powder suppresses airway inflammation in LPS and CS-induced post-infectious cough model mice via TRPA1/TRPV1 channels.

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.

Anti-inflammatory, analgesic, antitussive and antipyretic activities of polyphenol-enriched fraction from Nymphaea candida.

ETHNOPHARMACOLOGICAL RELEVANCE: "Snow-white waterlily" (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. AIM OF THE STUDY: Polyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. MATERIALS AND METHODS: The polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. RESULTS: NCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1ß, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. CONCLUSION: The experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.

Clinical characteristics and prognosis of laryngeal tuberculosis combined with respiratory tuberculosis.

PURPOSE: To investigate the clinical characteristics, diagnosis and prognosis of patients with laryngeal tuberculosis (LTB) combined with respiratory tuberculosis. MATERIALS AND METHODS: A retrospective analysis was conducted on 134 patients who underwent endoscopy and were eventually diagnosed with LTB. The patients' demographic characteristics, clinical manifestations, endoscopic features, auxiliary examination, imaging examination and prognostic characteristics were analyzed. RESULTS: LTB patients had a median age of 45.5 years (range from 12 to 87 years) and a median course of 3.0 months (range from 0.1 to 72 months). The patients' symptoms mainly presented as hoarseness (97.0 %), abnormal sensation of pharyngeal (49.3 %), cough and sputum (41.0 %), pharyngalgia (39.6 %), dysphagia (10.4 %) and dyspnea (8.2 %). The positive rate of tuberculous symptoms was 25.4 %. Endoscopic features showed that the lesions mainly involved the glottis (87.3 %), presenting as unilateral lesions (66.7 %), near-full-length involvement (88.0 %), with mucosal waves significantly reduced (86.3 %), followed by supraglottis (43.3 %), subglottis (24.6 %) and the pharynx (15.7 %). The lesions may present as granulomatous proliferation (66.4 %), ulceration (65.7 %) or swelling and exudation (51.5 %). A total of 75 patients (56.0 %) were finally diagnosed with combined pulmonary tuberculosis (PTB), with a positive chest X-ray rate of 25.6 % and a positive chest CT rate of 71.2 %. A total of 42 patients who received anti-tuberculosis treatment were followed up, and 73.8 % of patients had significant improvement in symptoms. The morphology of the pharyngeal and laryngeal mucosa returned to basically normal (59.4 %) or scar-like (34.4 %). CONCLUSIONS: LTB is usually found in middle-aged men, and patients' symptoms are mainly hoarseness, abnormal sensation of pharyngeal, pharyngalgia, cough and sputum, and can be combined with tuberculous symptoms. These lesions mainly involve multiple subregions, mainly in the glottis, and can be combined with pharyngeal involvement. There were various types of lesions. Half of the patients were complicated with PTB, and chest CT was superior to X-ray in the detection of pulmonary lesions. After regular anti-tuberculosis treatment, the symptoms and morphology of the pharyngeal and laryngeal mucosa of most patients were significantly improved.

Effects of nintedanib on symptoms in patients with progressive pulmonary fibrosis.

BACKGROUND: Dyspnoea and cough can have a profound impact on the lives of patients with pulmonary fibrosis. We investigated the effects of nintedanib on the symptoms and impact of pulmonary fibrosis in patients with progressive pulmonary fibrosis (PPF) in the INBUILD trial using the Living with Pulmonary Fibrosis (L-PF) questionnaire. METHODS: Patients had a fibrosing interstitial lung disease (ILD) (other than idiopathic pulmonary fibrosis) of >10% extent on high-resolution computed tomography (HRCT) and met criteria for ILD progression within the prior 24 months. Patients were randomised 1:1 to receive nintedanib or placebo. Changes in L-PF questionnaire scores from baseline to week 52 were assessed using mixed models for repeated measures. RESULTS: In total, 663 patients were treated. Compared with placebo, there were significantly smaller increases (worsenings) in adjusted mean L-PF questionnaire total (0.5 versus 5.1), symptoms (1.3 versus 5.3), dyspnoea (4.3 versus 7.8) and fatigue (0.7 versus 4.0) scores in the nintedanib group at week 52. L-PF questionnaire cough score decreased in the nintedanib group and increased in the placebo group (-1.8 versus 4.3). L-PF questionnaire impacts score decreased slightly in the nintedanib group and increased in the placebo group (-0.2 versus 4.6). Similar findings were observed in patients with a usual interstitial pneumonia-like fibrotic pattern on HRCT and in patients with other fibrotic patterns on HRCT. CONCLUSION: Based on changes in L-PF questionnaire scores, nintedanib reduced worsening of dyspnoea, fatigue and cough and the impacts of ILD over 52 weeks in patients with PPF.

Xingbei antitussive granules ameliorate cough hypersensitivity in post-infectious cough guinea pigs by regulating tryptase/PAR2/TRPV1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xingbei antitussive granules (XB) is a classic Chinese Medicine prescription for treating post-infectious cough(PIC), based on the Sanao Decoction from Formularies of the Bureau of People's Welfare Pharmacies in the Song Dynasty and Jiegeng decoction from Essentials of the Golden Chamber in the Han Dynasty. However, the therapeutic effects and pharmacological mechanisms are still ambiguous. In the present study, we endeavored to elucidate these underlying mechanisms. AIMS OF THE STUDY: This study aimed to explore the potential impact and mechanism of XB on PIC, and provide a scientific basis for its clinical application. MATERIALS AND METHODS: Cigarette smoking (CS) combined with lipopolysaccharide (LPS) nasal drops were administered to induce the PIC guinea pig with cough hypersensitivity status. Subsequently, the model guinea pigs were treated with XB and the cough frequency was observed by the capsaicin cough provocation test. The pathological changes of lung tissue were assessed by HE staining, and the levels of inflammatory mediators, mast cell degranulating substances, and neuropeptides were detected. The protein and mRNA expression of transient receptor potential vanilloid type 1(TRPV1), proteinase-activated receptor2(PAR2), and protein kinase C (PKC) were measured by Immunohistochemical staining, Western blot, and RT-qPCR. Changes in the abundance and composition of respiratory bacterial microbiota were determined by 16S rRNA sequencing. RESULTS: After XB treatment, the model guinea pigs showed a dose-dependent decrease in cough frequency, along with a significant alleviation in inflammatory infiltration of lung tissue and a reduction in inflammatory mediators. In addition, XB high-dose treatment significantly decreased the levels of mast cell Tryptase as well as ß-hexosaminidase (ß-Hex) and downregulated the expression of TRPV1, PAR2, and p-PKC. Simultaneously, levels of neuropeptides like substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and nerve growth factor (NGF) were improved. Besides, XB also can modulate the structure of respiratory bacterial microbiota and restore homeostasis. CONCLUSION: XB treatment alleviates cough hypersensitivity and inflammatory responses, inhibits the degranulation of mast cells, and ameliorates neurogenic inflammation in PIC guinea pigs whose mechanism may be associated with the inhibition of Tryptase/PAR2/PKC/TRPV1 and the recovery of respiratory bacterial microbiota.

Clinical features associated with pulmonary exacerbation diagnosis in infants and young children with cystic fibrosis.

RATIONALE: Diagnosing cystic fibrosis (CF) pulmonary exacerbations (PEx) in very young people with CF <3 years (VY-PwCF) is challenging because of the frequency of respiratory viral infections in this age group, and there are limited data on the clinical features associated with the diagnosis of PEx in this age group. The goal of this study was to identify clinical features associated with the diagnosis of PEx in VY-PwCF. METHODS: We reviewed the medical records of VY-PwCF followed at the Children's Hospital of Philadelphia born between 2013 and 2019. We collected data from all encounters with respiratory symptoms. PEx was defined by treatment with oral or intravenous antibiotics. Clinical features of PEx and non-PEx encounters were compared using descriptive statistics, and odds ratios of PEx diagnosis were calculated. RESULTS: A total of 78 patients were included in the analysis. The mean (SD) number of PEx per patient was 6.17 (5.88). The presence of a wet or nighttime cough and symptoms >3 days in duration were significantly associated with PEx diagnosis (p < .001). In contrast, symptoms such as sore throat or rhinorrhea were not associated with a higher likelihood of PEx. CONCLUSIONS: The presence of a wet or night-time cough and longer symptom duration are common features of PEx in VY-PwCF, whereas symptoms suggestive of upper respiratory viral infection are not. Our results will be helpful in counseling families of VY-PwCF in the signs and symptoms of PEx and in planning future research in PEx in this age group.

[Acute bronchitis - modern possibilities of mucactive therapy].

AIM: Analysis of the clinical effectiveness and safety of erdosteine use in comparison with standard (real practice) mucoactive therapy in patients with acute bronchitis (АВ) in adults. MATERIALS AND METHODS: The observational program included 100 adult patients with АВ, 50 of them (group 1) received erdosteine, the group 2 also included 50 patients who received acetylcysteine, bromhexine and other mucolytics (real clinical practice). The following were assessed: cough severity, average time for resolution of night and daytime cough, satisfaction with treatment, NO concentration in exhaled air, levels of C-reactive protein (CRP) and interleukin-6 (IL-6). RESULTS: The average duration of relief of severe daytime cough requiring continued therapy was: in group 1 - 3.7±0.46 days, night cough - 1.14±0.94 days. In the second group, daytime cough was relieved in 3.8±0.4 days, night cough - 1.08±0.7 days. The duration of mucoactive therapy in group 1 was 5.32±0.82 days, in group 2 this figure was 8.5±1.4 days (p<0.05). The number of АВ patients with a significant reduction in the severity of productive cough (1 point on cough severity scale) on the 6th day from the beginning of treatment in group 1 (erdosteine) amounted to 32 (64%), in group 2 - 27 (54%). Satisfaction with the treatment was higher in the group receiving erdosteine: according to the indicators "very satisfied" and "extremely satisfied" the patients of the group 1 - 42 - were the leaders in comparison with the group 2, where these positions were marked by 28 patients. The level of CRP in patients with АВ in group 1 was 24.7±21.24 mg/l, in group 2 - 16.37±16.5 mg/l, which indicates the viral etiology of the process and no need in the prescription of antimicrobial drugs. For the first time in Russian practice, the following were determined: the level of IL-6, which in the group 1 was 10.3±6.7 pc/ml; in the group 2 - 10.03±3.94 pc/ml; the level of exhaled NO in group 1 was 16.5±5.1 ppb, in group 2 - 14.9±4.6 ppb (the norm is up to 25 ppb). These indicators, against the background of mucoactive therapy, decreased to normal values by 6th day. CONCLUSION: The findings expand our understanding of АВ in adults. New results have been obtained on the role of CRP, IL-6 and NO in exhaled air during АВ. The use of erdosteine was accompanied by a significant mucoactive effect in the form of a pronounced regression of cough in patients with АВ compared to the comparison group in shorter term.

Assessment and Management of Cough in Idiopathic Pulmonary Fibrosis: A Narrative Review.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal disease with an unknown cause. It is characterized by symptoms such as cough and breathlessness, which significantly impact patients' quality of life. Cough, in particular, has emerged as a burdensome symptom for individuals with IPF. The etiology of cough in IPF patients is believed to be complex, involving factors related to the disease itself, such as increased sensitivity of cough nerves, lung structural changes, inflammation, and genetic factors, as well as comorbidities and medication effects. Unfortunately, effective treatment options for cough in IPF remain limited, often relying on empirical approaches based on studies involving chronic cough patients in general and the personal experience of physicians. Medications such as opioids and neuromodulators are commonly prescribed but have shown suboptimal efficacy, imposing significant physical, psychological, and economic burdens on patients. However, there is hope on the horizon, as specific purinergic P2 receptor ligand-gated ion channel (P2X3) inhibitors have demonstrated promising antitussive effects in ongoing clinical trials. This review aims to provide a comprehensive overview of the evaluation and management of cough in IPF patients, as well as highlight emerging pharmacological and non-pharmacological approaches that target the cough reflex and are currently being investigated in clinical settings.

Anti-inflammatory, anti-tussive effects and toxicity evaluation of Qingfei Dayuan granules.

OBJECTIVE: To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules (, QFDY), and to evaluate the acute and sub-chronic toxicity of QFDY. METHODS: Anti-inflammatory effects were evaluated by murine model of xylene induced ear edema in mice. Ear swelling degree was calculated and tumor necrosis factor-α, interleukin-1ß and interleukin-6 were determined. Anti-tussive evaluations were carried out in the mouse cough model induced by ammonia liquor. Latent period cough and number of cough within 3 min were counted. In acute toxicity study, the rats were randomly divided into test group and solvent control group. Body weighs, food intakes and general clinical signs were monitored. In the sub-chronic toxicity study, QFDY was administered to rats at 0, 4, 8 and 16 g/kg per day for 28 and 30 d of post treatment was conducted. Mortalities, clinical signs, body weight changes, food intakes, ophthalmological examinations, hematological parameters, biochemical indicators, electrolyte indicators, urinalyses and histopathological examinations were monitored. RESULTS: QFDY significantly inhibited the development of ear edema in anti-inflammatory assay and decreased cough frequency caused by ammonia liquor. The results presented a dose-effect relationship. In acute toxicity study, no abnormality exhibited at dose of 24.0 g/kg per day during the 14-d observation period. In the sub-chronic toxicity study, higher reticulocyte count, lymphocyte and lower Cl-, blood urea nitrogen were analyzed compared with the solvent control group. But the differences were considered to be incidental and not clinically toxic. Obvious dose-effect relationship of urine color was observed, and the three test groups at the end of the experiments resulted in significant increase in urobilinogen, bilirubin, ketone body and urine leukocyte. However, all the positive indicators returned to normal in the recovery period. Therefore, no toxicological changes were found during the study period. CONCLUSION: QFDY showed significant anti-inflammatory and anti-tussive effects in mice. The lethal dose (LD50) of per oral QFDY in rats was estimated to be more than 24.0 g/kg per day and the no observed adverse effect level was over 16 g/kg per day, which suggested that QFDY is relatively safe for oral medication at the present dose on rats. Our experimental results provide a reference for the further development and research of QFDY.

Evaluation and management of chronic cough in adults.

Background: Chronic cough (CC), a cough that lasts > 8 weeks, has an overall prevalence of 5-11% in adults, peaking between 60 and 80 years of age. Of the 15% of patients who remain undiagnosed or refractory to treatment, two thirds are women. Objective: The objective was to present an updated evidence-based algorithmic approach for evaluating and managing CC, with emphasis on treatment modalities for refractory CC. Methods: A literature search was conducted of medical literature data bases for guidelines, position papers, systematic reviews, and clinical trials from January 2022 to June 2023, on the evaluation and management of CC. Results: The initial assessment should be limited to a detailed history, physical examination, chest radiograph, spirometry, exhaled nitric oxide, blood eosinophil count, and measurement of cough severity and quality of life by using validated instruments. The top diagnoses to consider are asthma, chronic obstructive pulmonary disease, nonasthmatic eosinophilic bronchitis, gastroesophageal reflux disease, and upper airway cough syndrome. Additional studies are only obtained when red flags are present or the patient fails to respond after avoidance of high-risk factors, e.g., smoking and angiotensin-converting enzyme inhibitors, and 4-6 weeks of empiric treatment for the most likely respiratory and gastrointestinal diseases. When diagnostic tests and/or specific directed treatments fail to control CC, low-dose morphine (preferred), gabapentin, pregabalin, and/or cough control therapy are recommended. Non-narcotic purinergic 2×3 (P2×3) receptor antagonists, gafapixant and campilixant, are currently being studied for CC. Conclusion: For the evaluation and management of patients with CC, clinicians should use an algorithmic approach and identify "red flags," reduce high-risk factors, and use empiric treatment for the five top diagnoses before extensive diagnostic testing. Current treatment for refractory cough is limited to symptomatic management.

Conociendo las propiedades del Eucalipto, ¿un alivio para la tos? / Knowing the properties of Eucalyptus, ¿a cough relief?

El eucalipto se ha empleado popularmente para tratar afecciones respiratorias. Muchas veces en nuestras consultas como médicos de familia, los pacientes con problemas respiratorios nos preguntan sobre esta práctica y sus efectos en la salud. Por esto, decidimos hacer una búsqueda de la evidencia disponible. Luego de realizar una búsqueda bibliográfica y seleccionar la evidencia más reciente y de mejor calidad, podemos decir, que el eucalipto tuvo un efecto estadísticamente significativo en comparación con el placebo en cuanto a los síntomas relacionados con la tos como así también en su frecuencia. Igualmente, concluimos que estos efectos del eucalipto sobre la tos en procesos respiratorios agudos, deberían tomarse con precaución, siempre informando a nuestros pacientes sobre la evidencia actual limitada disponible, sin olvidar las creencias de cada persona para la toma de decisiones (AU)

Eucalyptus has been popularly used to treat respiratory conditions. Many times in our consultations as family doctors, patients with respiratory problems ask us about this practice and its effects on health. For this reason, we decided to do a search of the available evidence. After conducting a literature search and selecting the most recent and best-quality evidence, we can say that eucalyptus had a statistically significant effect compared to placebo in terms of cough-related symptoms as well as their frequency . Likewise, we conclude that these effects of eucalyptus on coughing in acute respiratory processes should be taken with caution, always informing our patients about the limited current evidence available, without forgetting each person's beliefs for decision-making (AU)

Effect of Montelukast Combined with Budesonide on Inflammatory Response and Pulmonary Function in Children with Cough Variant Asthma: A Meta-analysis.

This meta-analysis aimed to compare the efficacy of montelukast (MKST) combined with budesonide (BUD) and BUD alone in the treatment of pulmonary inflammation and pulmonary function in children with cough variant asthma (CVA). Five electronic databases were searched for studies about MKST+BUD therapy and BUD alone therapy on inflammation and pulmonary function in CVA children from inception to November 23, 2021. Twenty-two articles were included. The results showed that, compared with BUD alone, the combination treatment could achieve better improvement of pulmonary function and lower levels of inflammation (MKST+BUD group: FEV1: SMD = 2.77, 95% CI: 2.07, 3.46; FVC: SMD = 2.54, 95% CI: 1.82, 3.27; PEF: SMD = 2.27, 95% CI: 1.79, 2.75; IgE: SMD = -7.95, 95% CI: -9.66, -6.25; TNF-α: SMD = -4.67, 95% CI: -6.04, -3.31; IL-8: SMD = -8.18, 95% CI: -11.46, -4.90; BUD alone group: FEV1: SMD = 1.83, 95% CI: 1.34, 2.31; FVC: SMD = 1.39, 95% CI: 0.93, 1.84; PEF: SMD = 1.51, 95% CI: 1.13, 1.89; IgE: SMD = -4.93, 95% CI: -6.14, -3.72; TNF-α: SMD = -2.78, 95% CI: -3.76, -1.80; IL-8: SMD = -4.94, 95% CI: -7.10, -2.79). To conclude, compared with BUD alone, MKST+BUD therapy was found to be more effective in improving pulmonary function and reducing inflammation in CVA children. Key Words: Montelukast, Budesonide, Cough variant asthma, Children, Pulmonary function, Inflammatory markers, Meta-analysis.

Chronic cough relief by allosteric modulation of P2X3 without taste disturbance.

P2X receptors are cation channels that sense extracellular ATP. Many therapeutic candidates targeting P2X receptors have begun clinical trials or acquired approval for the treatment of refractory chronic cough (RCC) and other disorders. However, the present negative allosteric modulation of P2X receptors is primarily limited to the central pocket or the site below the left flipper domain. Here, we uncover a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and show that the antitussive effects of quercetin and PSFL2915 (our nM-affinity P2X3 inhibitor optimized based on quercetin) on male mice and guinea pigs were achieved by preventing allosteric changes of IP-HD in P2X3. While being therapeutically comparable to the newly licensed P2X3 RCC drug gefapixant, quercetin and PSFL2915 do not have an adverse effect on taste as gefapixant does. Thus, allosteric modulation of P2X3 via IP-HD may be a druggable strategy to alleviate RCC.

Identification of a New Pyrrolyl Pyridoindole Alkaloid, Melpyrrole, and Flazin from Honey and Their Cough-Suppressing Effect in Guinea Pigs.

The cough-suppressing effect of honey was demonstrated for the first time using a guinea pig model whereby cough was induced by citric acid and capsaicin, and a new pyrrolyl pyridoindole, 1-(5-(hydroxymethyl)-1H-pyrrol-2-yl)-9H-pyrido[3,4-b]indole-3-carboxylic acid (1), named melpyrrole, and flazin (2) were identified as the active principle components. The structures of 1 and 2 were estimated using a combination approach of an activity-guided survey and LC-MS/MS multivariate analysis and were finally established by total synthesis of 1 and comparison with an authentic standard for 2. Both compounds showed antitussive activity comparable to that of dextromethorphan in guinea pigs. Their antitussive effects were unaffected by an opioid antagonist and reversed by a nitric oxide (NO) synthase inhibitor, indicating that these natural products do not act directly on opiate receptors but through the NO signaling pathway.

Xiebai Zengye decoction improves respiratory function and attenuates inflammation in juvenile rats with postinfection cough via regulating ERK signaling pathway.

This study aimed to determine the effects of Xiebai Zengye decoction (XBZY) on airway inflammation and respiratory function in rats with postinfectious cough (PIC), and its regulatory effects on the extracellular signal-regulated kinase (ERK) signaling pathway. Compared with the normal group, the rats from the PIC group had significantly shortened expiratory time (TE) and enhanced pause (EEP), increased resistance (RT), and enhanced pause (Penh), along with increased levels of serum interleukin-4 (IL-4) and IL-6, and decreased levels of IL-10. The lung and colon tissues of rats from the PIC group showed histopathological changes, including inflammatory cell infiltration, damaged mucosal epithelium, and crypt structure, with significantly increased ERK mRNA and protein expression levels. Treatment with XBZY and montelukast sodium (MAS) improved the respiratory function and serum cytokine levels, reduced tissue inflammation, and decreased ERK mRNA and protein expression levels in the lung and colon tissues. In the lung tissues, XBZY treatment significantly decreased the expression of phosphorylated-ERK (p-ERK) protein, as well as p-MEK1/2, p-ERK1/2, and p-c-Fos proteins, while in the colon tissues, XBZY significantly decreased the expression of p-ERK1/2 and p-c-Fos proteins. However, MAS treatment only showed significant improvement in the lung tissue inflammation score, and the expression level of p-ERK protein in the lung tissue was decreased. In conclusion, the present study suggests that XBZY has a potential therapeutic effect on PIC by improving respiratory function and attenuating inflammation, and this effect may be associated with the inhibition of the ERK signaling pathway. These findings could provide a new direction for the development of treatments for PIC. However, further research is needed to elucidate the underlying molecular mechanisms of XBZY and to confirm its safety and efficacy in clinical trials.