Cough is a very common symptom causing medical consult. Several remedies are readily available in the market however these are currently not recommended among the pediatric population due to a few reasons which include the benign nature of acute cough, limited effectivity and lack of support from the United States Food and Drug Administration (USFDA) due to abuse potential.

We report a case of a 2-year-old male, no known co-morbidities with a 2 week history of upper respiratory tract infection. Initial assessment showed viral infection hence patient was given medications for symptomatic treatment. However, l week after, patient still presented with symptomatic persistent coughing that disrupted his activities of daily living, hence antitussive medication was already prescribed. After another 7 days, there was still persistence of symptoms, hence patient was given a trial medication of Pregabalin 0.7 milligram/kg/dose which noted instant cough relief one hour after the initial intake. Patient also reported to be more playful, improved sleep at night and improved appetite. Patient received total of 2 doses of Pregabalin in the span of 48 hours. On the third day, patient was still coughing but reported to be significantly less frequent and more productive, hence medication was then put on hold. Patient continuously improved after 5 more days and was eventually cough free.

This case report demonstrates the adequacy of Pregabalin as a supportive antitussive medication in a patient with an acute cough secondary to a viral infection.

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules. METHODS: The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CL^pro), papain like protease (PL^pro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CL^pro and PL^pro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis. RESULTS: Jingfang Granules exhibited 3CL^pro and PL^pro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 μg/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 μg/g, respectively. In addition, neohesperidin and naringin exhibited PL^pro inhibitory activities, and the inhibition rates at 8 μmol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CL^pro and PL^pro, and the inhibitory rates at 8 μmol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CL^pro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PL^pro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PL^pro. CONCLUSION Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CL^pro and PL^pro. The results are valuable for rational clinical use of Jingfang Granules.
Amino Acids ; Ammonia ; Antitussive Agents ; COVID-19 ; Chymases ; Coronavirus 3C Proteases ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cysteine Endopeptidases/metabolism* ; Humans ; Molecular Docking Simulation ; Papain ; Peptide Hydrolases ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Tandem Mass Spectrometry

This study aimed to investigate the anti-inflammatory, antitussive, expectorant, and anti-asthmatic effects of Qinbaohong Oral Liquid in mouse experiments and explore its action mechanism based on network pharmacology. The mouse auricle swelling was induced by xylene for detecting the anti-inflammatory effect of Qinbaohong Oral Liquid, whose antitussive effect was then examined in mice with cough after exposure to ammonium hydroxide. The expectorant effect was determined based on the excretion of phenol red into the mouse trachea. The mouse model of asthma induced by histamine phosphate and acetylcholine chloride was used to observe the anti-asthmatic effect. The chemical components of Qinbaohong Oral Liquid were retrieved from TCMSP and literature, followed by target prediction based on BATMAN-TCM. The targets of inflammation, cough, expectoration, and asthma collected from GeneCards were intersected with drug targets for GO and KEGG enrichment analysis using Metascape. The results were imported into STRING for exploring protein-protein interactions and screening the key targets. As demonstrated by our findings, Qinbaohong Oral Liquid at 4.5 and 9.0 mL·kg~(-1) obviously decreased the weight(P<0.05) and thickness(P<0.01) of the right swelling ear and also the weight diffe-rence(swelling degree) between the two ears(P<0.05), prolonged the incubation period of cough(P<0.05), reduced the frequency of cough within 3 min(P<0.05), and increased the excretion of phenol red into the mouse trachea(P<0.01). Qinbaohong Oral Li-quid at 2.3, 4.5, and 9.0 mL·kg~(-1) dramatically prolonged the incubation period of asthma(P<0.05). A total of 324 chemical components and 1 245 targets were harvested for the Qinbaohong Oral Liquid, together with 10 272 inflammation targets, 4 400 cough targets, 192 expectoration targets, and 7 533 asthma targets. Their intersection revealed that the anti-inflammatory, antitussive, expectorant and anti-asthmatic effects of Qinbaohong Oral Liquid were correlated with such GO biological processes as the regulation of ion transport and blood circulation and such KEGG pathways as cancer-related signaling pathways and neuroactive ligand-receptor interaction. Qinbaohong Oral Liquid has been confirmed by both experiments and network pharmacology analysis to be efficient in anti-inflammation, stopping cough, eliminating phlegm, and relieving asthma.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; Antitussive Agents/therapeutic use* ; Asthma/drug therapy* ; Cough/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Network Pharmacology

Levodropropizine is commonly used as an antitussive drug for acute and chronic cough. It is a non-opioid agent with peripheral antitussive action via the modulation of sensory neuropeptide levels in the airways. Thus, levodropropizine has a more tolerable profile than opioid antitussives. However, we experienced 3 cases of levodropropizine-induced anaphylaxis. Three patients commonly presented with generalized urticaria, dyspnea, and collapse after taking cold medication including levodropropizine. To find out the culprit drug, we performed skin tests, oral provocation tests (OPTs), and basophil activation tests (BATs). Two patients were confirmed as having levodropropizine-induced anaphylaxis by OPTs, and one of them showed positive to skin prick tests (SPTs). The other patient was confirmed by skin tests and BATs. When we analyzed pharmacovigilance data related to levodropropizine collected for 5 years, most cases (78.9%) had allergic reactions, such as rash, urticaria, angioedema, and anaphylaxis. Therefore, physicians should consider that levodropropizine can be a culprit drug, when anaphylaxis occurs after taking anti-cough or common cold medication.
Anaphylaxis* ; Angioedema ; Antitussive Agents ; Basophils ; Chiroptera ; Common Cold ; Cough ; Drug-Related Side Effects and Adverse Reactions ; Dyspnea ; Exanthema ; Humans ; Hypersensitivity ; Neuropeptides ; Pharmacovigilance ; Skin ; Skin Tests ; Urticaria

PURPOSE: This study aims to investigate the additive effect of the Hedera helix (HH) and Rhizoma coptidis (RC) extracts mixture on antitussive and expectorant activities in animals. MATERIALS AND METHODS: The expectorant assay was performed with phenol red secretion in mice trachea. Mice or guinea pigs were randomly divided into groups of 8 each, including negative and positive control groups. After gastric administration of the test extracts in mice, 2.5% phenol red solution (0.2 mL) was intraperitoneally injected. Trachea was dissected and optical density of tracheal secretion was measured. After gastric administration of the test extracts in guinea pigs, the antitussive activities were assessed using a citric acid-induced cough measurement. RESULTS: The extracts of HH and RC significantly increased tracheal secretion and inhibited cough. The mixture of HH and RC extracts in a 1:1 concentration at a dose of 200 mg/kg showed a more potent effect on phenol red secretion (25.25+/-3.14) and cough inhibition (61.25+/-5.36) than the individual use of each extracts [phenol red secretion; HH 13.39+/-4.22 (p=0.000), RC 20.78+/-2.50 (p=0.010), cough inhibition; HH 9.89+/-4.14 (p=0.010), RC 30.25+/-7.69 (p=0.000)]. A 3:1 ratio mixture of HH to RC demonstrated an optimal expectorant effect (p<0.001), and this mixture showed expectorant and antitussive effects in a dose-dependent manner. CONCLUSION: This study provides evidence for antitussive and expectorant effect of a 3:1 mixture of HH and RC, which may be a useful therapeutic option for respiratory diseases.
Animals ; Antitussive Agents/*administration & dosage/pharmacology/therapeutic use ; *Behavior, Addictive ; Cough/*drug therapy ; Drugs, Chinese Herbal/*administration & dosage/pharmacology/therapeutic use ; Ethanol ; Expectorants/*administration & dosage/pharmacology/therapeutic use ; Guinea Pigs ; Hedera/*chemistry/metabolism ; Male ; Mice ; Phytotherapy ; Plant Extracts/*pharmacology ; Plant Roots/chemistry ; Trachea/drug effects/metabolism

The common cold is an acute, self-limiting viral infection of the upper respiratory tract involving the nose, sinuses, pharynx and larynx. Drug therapies for the common cold are normally aimed at relieving the symptoms of the illness. Over-the-counter cough and cold medications should not be used in children younger than four years old because of potential harms and lack of benefit. Antibiotics, antitussives, anti-histamines, and inhaled corticosteroids are not effective in children. Products that may improve symptoms in children include expectorants, mucolytics, honey, vitamin C, zinc lozenges, geranium extract, and nasal saline irrigation. In adults, antihistamines, intranasal corticosteroids, codeine, intranasal ipratopium, and antibiotics are not effective. Decongestants, antihistamine/decongestant combi-nations, expectorants, and mucolytics may improve cold symptoms in adults. Nonsteroidal anti-inflammatory drugs and acetaminophen reduce pain secondary to upper respiratory tract infection in adults. Among complementary and alternative medicinetherapeutics, products containing vitamin C, zinc, or garlic may improve cold symptoms in adults. Prophylactic use of probiotics may decrease the frequency of colds in adults and children.
Acetaminophen ; Adrenal Cortex Hormones ; Adult ; Anti-Bacterial Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Antitussive Agents ; Ascorbic Acid ; Child ; Codeine ; Common Cold* ; Complementary Therapies ; Cough ; Drug Therapy* ; Expectorants ; Garlic ; Geranium ; Histamine Antagonists ; Honey ; Humans ; Larynx ; Nasal Decongestants ; Nonprescription Drugs ; Nose ; Pharynx ; Probiotics ; Respiratory System ; Respiratory Tract Infections ; Zinc

Chronic cough is a common symptom and the etiology of which can be challenging to diagnose. The key to successful management is to establish a diagnosis and to treat the cause of cough. Asthma, gastro-esophageal reflux, and postnasal drip syndrome have been thought to be most common causes of chronic cough. Various causes such as lung diseases (sarcoidosis, pertussis), obstructive sleep apnea, drug (angiotensin-converting enzyme inhibitor), and psychological status can induce chronic cough. However, many chronic cough patients do not have an identifiable cause. We need to understand the mechanisms underlying central and peripheral sensitization, how they interact with cough triggers and their relationship with the sensations that drive the urge to cough, and the subsequent motor cough response in chronic cough. Heightened cough reflex sensitivity is persistent and their cough is unexplained in many patients. In most patients who visited otorhinolaryngoloy clinics, it is possible to manage a majority of chronic cough patients successfully using a protocol based on presenting symptoms and therapeutic trials for the common causes of cough. However, there are few therapeutic options for patients with unexplained chronic cough. There is a pressing need to understand the physiological basis of unexplained chronic cough and to develop novel antitussive drugs that down regulate cough reflex sensitivity.
Adult* ; Antitussive Agents ; Asthma ; Cough* ; Diagnosis ; Gastroesophageal Reflux ; Humans ; Lung Diseases ; Reflex ; Respiratory Hypersensitivity ; Sensation ; Sleep Apnea, Obstructive

Aspergillus tracheobronchitis is a form of invasive pulmonary aspergillosis in which the Aspergillus infection is limited predominantly to the tracheobronchial tree. It occurs primarily in severely immunocompromised patients such as lung transplant recipients. Here, we report a case of Aspergillus tracheobronchitis in a 42-year-old man with diabetes mellitus, who presented with intractable cough, lack of expectoration of sputum, and chest discomfort. The patient did not respond to conventional treatment with antibiotics and antitussive agents, and he underwent bronchoscopy that showed multiple, discrete, gelatinous whitish plaques mainly involving the trachea and the left bronchus. On the basis of the bronchoscopic and microbiologic findings, we made the diagnosis of Aspergillus tracheobronchitis and initiated antifungal therapy. He showed gradual improvement in his symptoms and continued taking oral itraconazole for 6 months. Physicians should consider Aspergillus tracheobronchitis as a probable diagnosis in immunocompromised patients presenting with atypical respiratory symptoms and should try to establish a prompt diagnosis.
Adult ; Anti-Bacterial Agents ; Antitussive Agents ; Aspergillosis, Allergic Bronchopulmonary ; Aspergillus* ; Bronchi ; Bronchoscopy ; Cough ; Diabetes Mellitus ; Diagnosis ; Gelatin ; Humans ; Immunocompromised Host* ; Invasive Pulmonary Aspergillosis ; Itraconazole ; Lung ; Sputum ; Thorax ; Trachea ; Transplantation

The antitussive activity assay for the root extraction of Disporum cantoniense was carried out with coughing mice induced by ammonia liquor. The results showed that the ethanol and water extractions of D. cantoniense possess strong antitussive activity, and the high dose of the former was better than positive control, and then the constituents of the ethanol extraction were separated and purified by various modern chromatographic techniques. Their structures were identified by physico-chemical properties and spectroscopic data. As a result, eight compounds were isolated and identified as stigmast-4-en-3-one(1), (22E, 24R)-ergosta-5, 7, 22-trien-3beta-ol(2), obtucarbamate A(3), obtucarbamate B(4), neotigogenin(5), azo-2, 2'-bis[Z-(2,3-dihydroxy-4-methyl-5-methoxy) phenyl ethylene] (6),dimethyl {[carbonylbis (azanediyl)] bis( 2-methyl-5, 1-phenylene) j dicarbamate (7) , and quercetin-3-O-pB-D-glucopyranoside(8). All compounds were isolated from this plant for the first time, and the result of bioactivity-directed isolation showed that compounds 3, 4, and 6 had obvious effect on antitussive activity, and compound 6 had the same level as positive control.
Animals ; Antitussive Agents ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Ethanol ; chemistry ; Female ; Liliaceae ; chemistry ; Male ; Mice