The effect of oral guaifenesin on pediatric chronic rhinitis: A pilot study.

OBJECTIVES: To investigate the effectiveness of guaifenesin in the relief of nasal symptoms in children with chronic rhinitis (CR). We hypothesized that guaifenesin use over a 14-day study period would improve subjective nasal complaints in pediatric patients with chronic rhinitis, as measured by the SinoNasal-5 (SN-5) survey. We also hypothesized improvement in nasal volume and cross-sectional area with guaifenesin. STUDY DESIGN: Randomized, placebo-controlled, parallel group, masked clinical trial. METHODS: The study consisted of a 14-day, randomized, placebo-controlled, parallel group, masked clinical trial of oral guaifenesin for CR in children aged 7-18 years. A 2:1 ratio of subjects on active medication to placebo was used. The study was approved by the Western Institutional Review Board. On initial enrollment and at the conclusion of therapy, the SN-5 was completed by parents, acoustic rhinometry measurements performed, and mucus sampling for rheology was obtained. RESULTS: 30 subjects were enrolled in the study, with 20 receiving guaifenesin and 10 placebo. Treatment with guaifenesin for 14 days produced a significant mean change towards clinical improvement in SN-5 scores compared with placebo (p = 0.013). There was no significant difference in quality of life assessment scores between the two groups or in any of the acoustic rhinometry parameters. Many of the study subjects had difficulty producing a mucus sample sufficient for analysis. CONCLUSIONS: Based upon our pilot data, it appears that guaifenesin treatment may produce objective improvements in pediatric patients with CR. Further research with larger samples sizes, inclusion of children younger than 6, and biophysical mucus analyses is warranted. LEVEL OF EVIDENCE: Level 2b.

High throughput virtual screening strategy to develop a potential treatment for bronchial asthma by targeting interleukin 13 cytokine signaling.

Chronic inflammation in the airway passage leads to the clinical syndrome of pediatric asthma. Allergic reactions caused by bacterial, viral, and fungal infection lead to the immune dis-balance which primes T helper cells (Th2), a specific cluster of differentiation 4 (CD4) T cell differentiation. This favors the Th2-specific response by activating the inter-leukin 4/interleukin 13 (IL-4/IL-13) cytokine signaling and further activates the secretion of immunoglobulin E (IgE). IL-13 develops bronchial asthma by elevating bronchial hyperresponsiveness and enables production of immunoglobulin M (IgM) and IgE. The present study aims to target IL-13 signaling using molecular docking and understanding molecular dynamic simulation (MDS) to propose a compelling candidate to treat asthma. We developed a library of available allergic drugs (n=20) and checked the binding affinity against IL-13 protein (3BPN.pdb) through molecular docking and confirmed the best pose binding energy of -3.84 and -3.71 for epinephrine and guaifenesin, respectively. Studying the interaction of hydrogen bonds and Van der Walls, it is estimated that electrostatic energy is sufficient to interact with the active site of the IL-13 and has shown to inhibit inflammatory signaling. These computational results confirm epinephrine and guaifenesin as potential ligands showing potential inhibitory activity for IL-13 signaling. This study also suggests the designing of a new ligand and screening of a large cohort of drugs, in the future, to predict the exact mechanism to control the critical feature of asthma.

Plasma histamine concentrations in horses administered sodium penicillin, guaifenesin-xylazine-ketamine and isoflurane with morphine or butorphanol.

OBJECTIVE: Various drugs administered to horses undergoing surgical procedures can release histamine. Histamine concentrations were evaluated in horses prepared for surgery and administered butorphanol or morphine intraoperative infusions. STUDY DESIGN: Prospective studies with one randomized. ANIMALS: A total of 44 client-owned horses. METHODS: In one study, anesthesia was induced with xylazine followed by ketamine-diazepam. Anesthesia was maintained with guaifenesin-xylazine-ketamine (GXK) during surgical preparation. For surgery, isoflurane was administered with intravenous (IV) morphine (group M: 0.15 mg kg-1 and 0.1 mg kg-1 hour-1; 15 horses) or butorphanol (group B: 0.05 mg kg-1 and 0.01 mg kg-1 hour-1; 15 horses). Histamine and morphine concentrations were measured using enzyme-linked immunoassay before opioid injection (time 0), and after 1, 2, 5, 30, 60 and 90 minutes. In a subsequent study, plasma histamine concentrations were measured in 14 horses before drug administration (baseline), 15 minutes after IV sodium penicillin and 15 minutes after starting GXK IV infusion. Statistical comparison was performed using anova for repeated measures. Pearson correlation compared morphine and histamine concentrations. Data are presented as mean ± standard deviation. Significance was assumed when p ≤ 0.05. RESULTS: With histamine, differences occurred between baseline (3.2 ± 2.4 ng mL-1) and GXK (5.2 ± 7.1 ng mL-1) and between baseline and time 0 in group B (11.9 ± 13.4 ng mL-1) and group M (11.1 ± 12.4 ng mL-1). No differences occurred between baseline and after penicillin or between groups M and B. Morphine concentrations were higher at 1 minute following injection (8.1 ± 5.1 ng mL-1) than at 30 minutes (4.9 ± 3.1 ng mL-1) and 60 minutes (4.0 ± 2.5 ng mL-1). Histamine correlated with morphine at 2, 30 and 60 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: GXK increased histamine concentration, but concentrations were similar with morphine and butorphanol.

Therapeutic effect of chlorpheniramine in treatingupper airway cough syndrome (UACS) and chronic rhinitis/sinusitis.

This paper aims to analyze the specific effect of chlorpheniramine on upper airway cough syndrome is related to its treatment of chronic rhinitis and sinusitis. A total of 218 patients admitted to hospital between March 2014 and June 2016 were treated with chlorpheniramine. The patients were divided into two groups based on treatment effect in follow-up visits (all were effective): effective group (114 cases, 52.29%) and ineffective group (104 cases, 47.71%). The proportion of complicated rhinitis or sinusitis of the two groups were compared, and improvement effect on clinical symptoms of chronic rhinitis and sinusitis after treatment was compared. The probability of rhinitis / sinusitis was 65.79% (75/114) in the effective group and 69.23% (72/104) in the ineffective group. There was no statistical difference between the two groups (P>0.05). In both effective and ineffective group, the symptoms such as chest tightness and shortness of breath and pharyngeal discomfort were improved to a certain extent, and the effective group had better improvement effect, but there was no statistical difference between the two groups (P>0.05). In addition, there was no correlation between improvement of cough and improvement of symptoms in the effective group, 21 cases of cough disappeared completely, while complete disappearance rate of other symptoms was only 57.15% (12/21). Chlorpheniramine is effective to some extent in treatment of upper airway cough syndrome, but chlorpheniramine in treatment of upper airway cough syndrome is not associated with rhinitis/sinusitis treatment.

Honey plus coffee versus systemic steroid in the treatment of persistent post-infectious cough: a randomised controlled trial.

BACKGROUND: Persistent post-infectious cough (PPC) is a cough that remains after a common cold or an upper respiratory tract infection for more than three weeks or perhaps for many months. Two of the suggested treatments for PPC are systemic steroid and honey plus coffee. AIMS: The aim of this study was to evaluate and compare scientifically the therapeutic effects of these two regimens. METHODS: A double-blind randomised controlled trial was conducted from 2008 to 2011 at the Baqiyatallah University Hospital, Tehran, Iran. Included in the study were 97 adults who had experienced PPC for more than three weeks. Patients with other causes of chronic cough, systemic disease, or abnormal routine laboratory tests were excluded. The participants were distributed into three groups. A jam like paste was prepared which consisted of honey plus coffee for the first group ('HC'), prednisolone for the second group (steroid, 'S'), and guaifenesin for the third group (control, 'C'). The participants were told to dissolve a specified amount of their product in warm water and to drink the solution every eight hours for one week. All the participants were evaluated before treatment and one week after completion of treatment to measure the severity of their cough. The main outcome measure was the mean cough frequency before and after one week's treatment calculated by a validated visual analogue cough questionnaire score. RESULTS: There were 97 adult patients (55 men) enrolled in this study with the mean of age of 40.1 years. The mean (+/- SD) cough scores pre- and post-treatment were: HC group 2.9 (0.3) pre-treatment and 0.2 (0.5) post-treatment (p < 0.001); steroid ('S') group 3.0 (0.0) pre-treatment and 2.4 (0.6) post-treatment (p < 0.05); control ('C') group 2.8 (0.4) pre-treatment and 2.7 (0.5) post-treatment (p > 0.05). Analysis of variance showed a significant difference between the mean cough frequency before and after treatment in the HC group versus the S group (p< 0.001). Honey plus coffee was found to be the most effective treatment modality for PPC. CONCLUSIONS: A combination of honey and coffee can be used as an alternative medicine in the treatment of PPC.

[Use of the mucoregulator ascoril for respiratory diseases].

The paper deals with the use of the combined mucoregulatory drug ascoril in pulmonological care. Due to its multicomponent composition, the drug has mucoregulatory properties that combine a bronchodilator effect and an ability to dilute sputum and to synthesize the surfactant. The mechanism of action of each ascoril component is analyzed; the results of basic experimental and clinical studies on the use of the drug are given. A wide range of indications, such as respiratory system diseases, for ascoril use is demonstrated.

Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm.

In Duchenne muscular dystrophy (DMD), palliative glucocorticoid therapy can produce myopathy or calcification. Since increased nitric oxide synthase activity in dystrophic mice promotes regeneration, the outcome of two nitric oxide (NO) donor drugs, MyoNovin (M) and isosorbide dinitrate (I), on the effectiveness of the anti-inflammatory drug prednisone (P) in alleviating progression of dystrophy was tested. Dystrophic mdx mice were treated (18 days) as controls or with an NO donor ± P. Fiber permeability and DNA synthesis were labeled by Evans blue dye (EBD) and bromodeoxyuridine uptake, respectively. P decreased body weight gain, M increased quadriceps mass, and I increased heart mass. P increased fiber permeability (%EBD+ fibers) and calcification in diaphragm. Treatment with NO donors + P (M+P, I+P) reduced %EBD+ fibers and calcification vs. P alone. %EBD+ fibers in M+P diaphragm did not differ from control. NO donor treatment reduced proliferation and the population of c-met+ cells and accelerated fiber regeneration. Concurrent with P, NO donor treatment suppressed two important detrimental effects of P in mice, possibly by accelerating regeneration, rebalancing satellite cell quiescence and activation in dystrophy, and/or increasing perfusion. Results suggest that NO donors could improve current therapy for DMD.

Recommendations for the proper use of nonprescription cough suppressants and expectorants in solid-organ transplant recipients.

OBJECTIVE: To describe the pharmacology and safety of oral over-the-counter cough suppressants and expectorants and to present recommendations for the use of these agents in solid-organ transplant recipients based on the potential for adverse drug reactions or drug-disease interactions. DATA SOURCES AND EXTRACTION: Data from journal articles and other sources describing the pharmacology and safety of over-the-counter cough suppressants and expectorants, drug-drug interactions with immunosuppressive agents, and drug-disease state interactions are reviewed. DATA SYNTHESIS: Potential and documented drug-drug interactions between immunosuppressive agents and over-the-counter cough medications guaifenesin, dextromethorphan, diphenhydramine, and codeine were evaluated on the basis of pharmacokinetic and pharmacodynamic principles. Interactions between these cough medications and the physiological changes in the body following transplantation also were examined. CONCLUSION: Diphenhydramine requires additional monitoring when used to treat cough in transplant recipients owing to its anticholinergic properties and the potential for interactions with cyclosporine. Dextromethorphan can be used in most transplant recipients, although greater caution should be exercised if the patient has undergone liver transplant or has liver impairment. Guaifenesin can be used in transplant recipients but should be used with caution in patients receiving kidney or lung transplants and in patients with renal impairment. Codeine combined with guaifenesin is another option for cough and can be used in most transplant patients although those with reduced renal function should be monitored carefully for adverse events.

Guaifenesin in rhinitis.

Mucus in the airways is a complex mixture of water, lipids, glycoproteins, sugars, and electrolytes that serves as a lubricant for the epithelium. The efficient flow of respiratory mucus is a first level of immune defense that requires an appropriate viscosity and elasticity for optimal barrier and ciliary functions. Thickening and drying of airway mucus by respiratory tract infections, allergies, and drugs can impair evacuation. Tenacious, bothersome mucus is an annoying and frequent symptom of rhinitis that is difficult to manage. Common remedies include adequate hydration through fluid intake and nasal washes. The use of mucoactive agents is controversial due to limited data and equivocal efficacy in available studies. Nonetheless, some patients benefit. This review examines the use of guaifenesin (glyceryl guaiacolate) on bothersome nasal mucus associated with rhinitis, including the available published data and clinical experience.

High throughput virtual screening strategy to develop a potential treatment for bronchial asthma by targeting interleukin 13 cytokine signaling

Chronic inflammation in the airway passage leads to the clinical syndrome of pediatric asthma. Allergic reactions caused by bacterial, viral, and fungal infection lead to the immune dis-balance which primes T helper cells (Th2), a specific cluster of differentiation 4 (CD4) T cell differentiation. This favors the Th2-specific response by activating the inter-leukin 4/interleukin 13 (IL-4/IL-13) cytokine signaling and further activates the secretion of immunoglobulin E (IgE). IL-13 develops bronchial asthma by elevating bronchial hyperresponsiveness and enables production of immunoglobulin M (IgM) and IgE. The present study aims to target IL-13 signaling using molecular docking and understanding molecular dynamic simulation (MDS) to propose a compelling candidate to treat asthma. We developed a library of available allergic drugs (n=20) and checked the binding affinity against IL-13 protein (3BPN.pdb) through molecular docking and confirmed the best pose binding energy of –3.84 and –3.71 for epinephrine and guaifenesin, respectively. Studying the interaction of hydrogen bonds and Van der Walls, it is estimated that electrostatic energy is sufficient to interact with the active site of the IL-13 and has shown to inhibit inflammatory signaling. These computational results confirm epinephrine and guaifenesin as potential ligands showing potential inhibitory activity for IL-13 signaling. This study also suggests the designing of a new ligand and screening of a large cohort of drugs, in the future, to predict the exact mechanism to control the critical feature of asthma (AU)

The role of mucoactive agents in the mechanically ventilated patient: a review of the literature.

INTRODUCTION: The management of airway secretions in the mechanically ventilated patient is a routine task throughout all intensive care units. The current treatment strategies are primarily based on anecdotal experiences rather than statistical evidence. Areas covered: This review article evaluates the data from published trials surrounding mucoactive agents and their use in the critically ill patient population. We completed an extensive search through PUBMED and CINAHL via EBSCO, along with the Cochran library to find all trials using mucoactive agents in the critically ill patient population. Expert commentary: Overall, the role of mucoactive agents in the intensive care unit is a field within pulmonary critical care that is in need of evidence-based recommendations. We feel that there is great opportunity for investigators to evaluate different mucoactive therapies in this patient population and to determine their effect on clinical outcomes.

Guaiphenesin-ketamine-xylazine infusion to maintain anesthesia in mules undergoing field castration.

BACKGROUND: In order to determine whether a combination of guaiphenesin, ketamine and xylazine can induce safe and satisfactory anaesthesia in mules undergoing field castration, eight healthy adult intact male mules were employed. They were premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of xylazine (0.3 mg/kg IV) was administered in case of inadequate depth of sedation. Anaesthesia was induced with IV thiopental (6 mg/kg). The quality of sedation and induction was recorded. Anaesthesia was maintained with an infusion of guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and haemoglobin oxygen saturation (SpO2) were measured every 5 min. The data were analysed with simple one-way analysis of variance (ANOVA). A P value < 0.05 was considered statistically significant. Time of anesthesia, time of surgery and time of recovery were recorded. RESULTS: Only one mule required an additional dose of xylazine to achieve a satisfactory depth of sedation. Thiopental at the dose of 6 mg/kg IV resulted in smooth induction and lateral recumbency in all animals. GKX provided adequate anaesthesia to perform castration in all mules. Muscle relaxation was deemed adequate and physiological variables remained stable and within references values during the anaesthesia and did not change in response to surgical stimulation. Time (mean ± standard deviation) from the end of the infusion to sternal recumbency and time from sternal recumbency to standing were 27.7 ± 4.6 and 30.1 ± 7.7 min, respectively. CONCLUSIONS: The combination of xylazine, thiopental and GKX provides satisfactory short-term anaesthesia in mules undergoing field castration.

Effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy.

OBJECTIVE: The objective of this prospective, randomized, controlled study (N = 28) was to evaluate the effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy. METHODS: Patients were selected based on a clinical history consistent with postviral vagal neuropathy and a history of an antecedent upper respiratory tract infection. All patients had been tried on antireflux medication (proton pump inhibitors) and had a negative chest x-ray before presentation. All were nonsmokers without a history of asthma. Patients on angiotensin-converting enzyme inhibitors were excluded from the study. All patients completed a pretreatment, validated cough-specific quality-of-life (QOL) survey. Patients were randomized by chart numbers to either 10 mg amitriptyline at bedtime or 10 to 100 mg/5 mL, 10 mL codeine/guaifenesin every 6 hours standing dose while awake. Both groups were instructed to complete 10 days of therapy and then asked to subjectively rate the reduction in the frequency and severity of their cough by 100%, 75%, 50%, 25%, or 0% as well as completing the posttreatment cough QOL questionnaire. Those patients experiencing a 75% to 100% reduction were recorded as having a complete response, 25% to 50% a partial response, and 0% as having no response. Final results and the cough QOL survey were recorded and used for statistical analysis. RESULTS: A majority of patients in the amitriptyline group achieved a complete response on the initial dose of 10 mg. None of the codeine/guaifenesin group achieved a complete response. The data were analyzed using a logistic regression model, and amitriptyline was found to be a highly significant predictor of a greater than 50% response when compared with codeine/guaifenesin (P = .0007). The same data were analyzed using a proportional odds model and similar results were noted. CONCLUSIONS: Chronic cough can have a profound impact on the psychosocial function of patients. The most common causes of a persisting cough in the absence of infection or chronic smoking are laryngopharyngeal reflux, asthma, particularly the cough variant, allergy, rhinosinusitis, bronchitis, and medications, in particular angiotensin-converting enzyme inhibitors. Currently, there are few effective treatments for cough with an acceptable therapeutic ratio and more selective drugs with a more favorable side effect profile are needed. This is this first prospective, randomized, controlled study comparing the effectiveness of amitriptyline versus codeine/guaifenesin for select cases of chronic cough resulting from suspected postviral vagal neuropathy.

Cough. A comprehensive review.

An understanding of the anatomic, physiologic, and pathophysiologic aspects of cough is necessary to appropriately diagnose and treat patients with cough. In the majority of persons, cough that is acute and self-limiting is usually secondary to a viral upper respiratory tract infection; cough that is chronic and persistent is usually due to chronic bronchitis or postnasal drip. In the remaining persons, to determine the cause of cough, it is necessary to systematically consider anatomic locations were receptors and afferent nervous pathways are located. Definitive treatment of cough depends on determining its precise cause and then initiating specific therapy for the underlying disorder. Only when the cause of cough remains unknown or when cough performs no useful function and its complications represent a potential hazard to the patient, should symptomatic treatment be considered. Combination cough preparations should not be prescribed.

Effect of a single 1200 Mg dose of Mucinex® on mucociliary and cough clearance during an acute respiratory tract infection.

BACKGROUND: Observational studies suggest that orally administered guaifenesin (GGE) may thin lower respiratory tract secretions but none have examined its effects on mucociliary and cough clearance (MCC/CC) during a respiratory tract infection (RTI). The current study was a randomized, parallel-group, double-blind, placebo-controlled study in non-smoking adults who suffered from an acute upper RTI. METHODS: We assessed the effects of a single dose of Mucinex(®) 1200 mg (2 × 600 mg extended release tablets) (ER GGE) on 1) MCC/CC by assessing the rate of removal from the lung of inhaled radioactive tracer particles (Tc99m-sulfur colloid), 2) sputum dynamic rheology by stress/strain creep transformation over the linear part of the curve, 3) sessile drop interfacial tension by the deNouy ring technique, and 4) subjective symptom measures. MCC was measured during the morning (period 1) and compared to that in the afternoon 4 h later (period 2) immediately following either drug (n = 19) or placebo (n = 19). For both period 1 and 2 subjects performed 60 voluntary coughs from 60 to 90 min after inhalation of radio-labeled aerosol for a measure of CC. Sputum properties were measured from subjects who expectorated sputum during the cough period post treatment (n = 8-12 for each cohort). RESULTS: We found no effect of ER GGE on MCC or CC compared to placebo. MCC through 60 min for period 1 vs. 2 = 8.3 vs. 11.8% (placebo) and = 9.7 vs. 11.1% (drug) (NS) and CC for period 1 vs. 2 was 9.9 vs. 9.1% (placebo) and 10.8 vs. 5.6% (drug) (NS). There was no significant difference in sputum biophysical properties after administration of drug or placebo. CONCLUSIONS: There was no significant effect of a single dose of ER GGE on MCC/CC or on sputum biophysical properties compared to placebo in this population of adult patients with an acute RTI. ClinicalTrials.gov Identifier: NCT01114581.

Effect of guaifenesin on cough reflex sensitivity.

BACKGROUND: Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. STUDY OBJECTIVES: To evaluate the effect of guaifenesin on cough reflex sensitivity. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Academic medical center. PARTICIPANTS: Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. INTERVENTIONS: On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 h after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. MEASUREMENTS AND RESULTS: The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. CONCLUSIONS: Our results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Antitussive effect of guaifenesin in young adults with natural colds. Objective and subjective assessment.

The efficacy of guaifenesin in reducing cough frequency in young adults with acute respiratory disease was evaluated by both an objective cough counting system and a questionnaire. A guaifenesin cough preparation and the syrup vehicle were administered in a double-blind manner. Coughs were recorded on tape over a 24-hour baseline evaluation period and a 36-hour treatment period for 42 patients. A pronounced diurnal variation in cough frequency was observed. The evaluation of efficacy was based upon comparisons between equivalent six-hour time periods of successive days. No antitussive effect of guaifenesin was demonstrated. The questionnaire was administered to 65 patients, including the 42 whose coughs were recorded. Of 26 patients with productive cough receiving guaifenesin, 25 (96 percent) reported a decrease in sputum thickness compared to 13 (54 percent) of 24 patients receiving the vehicle (p = 0.01, Fisher exact test). Twenty-three of 26 (88 percent) patients receiving guaifenesin also reported reduction in sputum quantity compared to 15 of 24 (62.5 percent) receiving the vehicle (p = 0.07, Fisher exact test). The diurnal variation in cough frequency measured by the tape recording was not apparent from the subjective cough frequency estimates obtained by the questionnaire.