Effects of Guaifenesin on Nasal Mucociliary Clearance and Ciliary Beat Frequency in Healthy Volunteers

doi:10.1378/chest.107.3.747

Chest

Volume 107, Issue 3, March 1995, Pages 747-751

https://doi.org/10.1378/chest.107.3.747 Get rights and content

Study objective

Mucociliary clearance is an important host defense function of the upper respiratory tract that requires the coordinated beating of cilia and results in the transport of mucus to the oropharynx. Guaifenesin is a commonly prescribed drug that is reported to improve the clearance of respiratory secretions. We hypothesized that guaifenesin increases nasal mucociliary clearance related to increases in ciliary beat frequency (CBF) and that a direct relationship exists between nasal CBF and nasal mucociliary clearance.

Design

Double-blind placebo-controlled crossover study.

Participants

Ten healthy volunteers with a previous history of sinus disease.

Interventions

Subjects received guaifenesin or placebo on days 1 to 7 or days 14 to 21.

Measurements and Results

In vivo saccharine transit time (STT) was measured by noting the time in minutes required for the subject to taste a saccharin particle placed on the inferior turbinate of the naris. The CBF was determined by video microscopy on ten separate groups of beating ciliated nasal mucosal cells obtained by brushing immediately after each STT determination. We found that there was no significant change between the guaifenesin- or placebo-treated groups from baseline values of STT (p=0.94) or CBF (p=0.46). Regression analysis demonstrated no relationship between STT and CBF for repeated measures within subjects (mean r²=0.18; mean p=0.66) and between STT and CBF when all paired measurements were combined across subjects (r²=0.47; p=0.46).

Conclusion

We conclude that guaifenesin exerts no measurable effect on in vivo nasal mucociliary clearance or ex vivo nasal ciliary motility in healthy volunteers with previous sinus disease. In addition, there appears to be no relationship between nasal STT measured in vivo and CBF measured ex vivo. The lack of correlation is most likely due to variations in CBF related to sampling artifacts introduced by the nasal brushing process.

Section snippets

Clinical Data

Subject Recruitment: The study protocol was approved by the Institutional Review Board at the University of Nebraska Medical Center prior to subject accrual. Ten healthy volunteers with a history of previous sinus problems were recruited through an advertisement to participate in the study. All subjects had no active sinus infection, nasal or sinus discharge, fevers, nasal stuffiness, or other active symptoms at the time of the study. Originally 12 subjects started the study, but one subject

Effect of Guaifenesin and Placebo on Saccharin Transit Time

The effect of guaifenesin was examined by STT. The baseline STT for individuals prior to guaifenesin and following 7 days on 2,000 mg/d was not significantly different (pre, 14.9 ± 1.2 min vs post, 14.1 ± 1.7 min; p=0.31; Fig 2, A). Similarly, there was no significant difference between the STT measured before and at the end of the placebo period of 7 days (pre, 16.8 ± 2.1 min vs post, 15.5 ± 1.2 min; p=0.28; Fig 2, B). When the change over seven days of treatment for guaifenesin was compared

Discussion

Our study examined the effect of guaifenesin on mucociliary clearance as measured in vivo by nasal STT and on ciliary motility as measured ex vivo by CBF. We found that guaifenesin had no significant effect on either of these measures of nasal mucociliary function. Our observation bolsters the experience in the literature in which few well designed studies have shown that guaifenesin promotes mucociliary clearance. Thomson and coworkers³ found that guaifenesin had a small but positive effect on

ACKNOWLEDGMENTS

The authors thank Proctor and Gamble for their sponsorship of this study. We also wish to acknowledge Kathryn May for her valuable technical assistance in performing the nasal brushings and CBF measurements and the nursing staff of the Otolaryngology Clinic for assisting in subject accrual and the nasal STT determinations.

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There are more references available in the full text version of this article.

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Mucoactive drugs and multiple applications in pulmonary disease therapy
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Mucus is a complex polymeric hydrogel that serves as a critical defense in several organs. In the lungs, it provides a formidable barrier against inhaled particles such as microorganisms. In addition, mucus is essential for normal lung physiology, as it promotes immune tolerance and facilitates a normal commensal pulmonary microbiome. Hypersecretion of airway mucus is a characteristic of numerous respiratory diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and Cystic Fibrosis (CF), and creates pulmonary obstruction, limiting the effectiveness of inhaled therapies. Due to those alterations, therapeutic strategies must be optimal to limit airway obstruction and restore pulmonary function. Mucoactive drugs are common therapeutic options and are classified into different groups depending on their modes of action, i.e., expectorants, mucokinetics, mucoregulators and mucolytics. This review focuses on mucoactive drugs and their modes of action. A special focus will be made on two challenging pulmonary pathologies: COPD and CF, and on their clinical studies conducted with mucoactive drugs.
Effect of a single 1200 Mg dose of Mucinex<sup>®</sup> on mucociliary and cough clearance during an acute respiratory tract infection
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The mechanism or time course by which guaifenesin may help clear secretions from the lungs is unclear and the evidence for its efficacy in improving MCC/CC of lower respiratory tract secretions is limited [1–4]. Early studies to assess the effect of guaifenesin on mucociliary or cough clearance (MCC/CC) showed conflicting results [4–6] but none have examined its effects during an RTI. Accordingly, the current study was designed to test the hypothesis that GGE would improve MCC/CC in non-smoking adults during an acute RTI.
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.
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).
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.
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
Other mucoactive agents for cystic fibrosis
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One subclass of expectorants is the classic expectorants, which are intended to increase sputum volume via a vagal gastric reflex. The agents that have been studied, guaifenesin and iodide-containing agents, have not been found to have worthwhile clinical effects on mucus clearance.27–29 These compounds have not been the subject of further investigation.
This review examines specific mucoactive agents from three classes: expectorants, which add water to the airway; ion-transport modifiers, which promote ion and water transport across the epithelium of the airway; and mucokinetics, which improve cough-mediated clearance by increasing airflow or reducing sputum adhesivity. The agents are isotonic and hypertonic saline, mannitol, denufosol and β-agonists. Our understanding of these agents has recently improved through pre-clinical research, clinical trials and, in particular, extensive research into the nature of the liquid lining the surface of the airway, both in health and in cystic fibrosis (CF). For each agent, recent research is reviewed, highlighting the evidence for possible mechanisms of action and for clinical efficacy in CF, as well as the implications for the optimal clinical application of the agent.
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2019, Nefrologia
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Time between the placement of saccharin and first sensation of sweet taste on the tongue is measured with a timer.13 Broad range of times for normal MC have been reported in the literature from 4.4 to 20 min.14–17 If there was no perception within 30 min, another saccharin particle was placed directly on the tongue to determine if the patient tastes saccharin at all.
Mucociliary clearance (MC) is a critical defense mechanism for the protection of the entire respiratory system. Nasal colonization of some pathogens and chronical nasal infections are important risk factors for peritonitis. Any disturbance in the MC causes stasis of secretions and secondary infections.
The aim of the study was to evaluate the patients with chronic kidney disease (CKD) receiving continuous ambulatory peritoneal dialysis (CAPD) in terms of nasal MC. More specifically, the goal is to investigate the possible correlation between the nasal MC and peritonitis.
Forty CAPD patients and 39 healthy volunteers were involved in the study. The nasal MC was evaluated with the saccharin test, in which a 1 mm diameter saccharin particle was carefully placed on the antero-medial surface of inferior nasal concha. The time taken by the subjects from the placement of particle to the perception of the sweet taste was taken as mucociliary clearance time (MCT). The groups were compared in terms of MCT. The patient group was evaluated in terms of a peritonitis history, and the correlations with MC were analyzed.
Patient group with CKD consisted of 16 females and 24 males with a mean age of 32.4 years; healthy individuals in the control group consisted of 17 women and 22 men with a mean age of 33.3 years. There was not a significant difference in terms of mean MC time in patients with CKD when compared with the individuals in the control group. The comparison between the mean MCT in the patients who had a history of peritonitis and patients without peritonitis was statistically significant (p < 0.05).
Unique for being conducted with patients in continuous ambulatory peritoneal dialysis, the current study shows that although the MC of CKD patients and healthy individuals is similar, patients with low rates of MC appear to present an increased incidence of peritoneal infection. Considering the small sample investigated, an invitation to future confirmatory studies would be appropriate.
El aclaramiento mucociliar (AM) es un mecanismo de defensa fundamental para la protección del sistema respiratorio. La colonización nasal de algunos patógenos y las infecciones nasales crónicas son factores de riesgo importantes de peritonitis. Cualquier alteración en el AM provoca estasis de secreciones e infecciones secundarias.
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El grupo de pacientes con NC constó de 16 mujeres y 24 hombres con una media de edad de 32,4 años. Los pacientes sanos en el grupo control fueron 17 mujeres y 22 hombres con una media de edad de 33,3 años. No se observó una diferencia significativa en el tiempo medio de AM en pacientes con NC respecto a los pacientes del grupo control. La comparación entre el TAM medio en los pacientes con antecedentes de peritonitis y en pacientes sin peritonitis fue estadísticamente significativa (p < 0,05).
Único por llevarse a cabo en pacientes con diálisis peritoneal ambulatoria continua, el estudio actual muestra que, aunque el AM de pacientes con NC y pacientes sanos es similar, los pacientes con tasas bajas de AM parecen presentar un aumento de la incidencia de infección peritoneal. Teniendo en cuenta la pequeña muestra estudiada, consideramos conveniente realizar nuevos estudios de confirmación.
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Clinical Investigations: Miscellaneous: ArticlesEffects of Guaifenesin on Nasal Mucociliary Clearance and Ciliary Beat Frequency in Healthy Volunteers

Study objective

Design

Participants

Interventions

Measurements and Results

Conclusion

Section snippets

Clinical Data

Effect of Guaifenesin and Placebo on Saccharin Transit Time

Discussion

ACKNOWLEDGMENTS

J Allergy Clin Immunol

The immotile cilia syndrome and other ciliary diseases

Int Rev Exp Pathol Acta Cytologica

The role of guaifenesin in the treatment of sinonasal disease in patients infected with the human immunodeficiency virus (HIV)

Laryngoscope

Clinical Investigations: Miscellaneous: Articles
Effects of Guaifenesin on Nasal Mucociliary Clearance and Ciliary Beat Frequency in Healthy Volunteers