Physiology and Pathophysiology of Human Airway Mucus

The mucus clearance system is the dominant mechanical host defense system of the human lung. Mucus is cleared from the lung by cilia and airflow, including both two-phase gas liquid pumping and cough-dependent mechanisms, and mucus transport rates are heavily dependent on mucus concentration. Importantly, mucus transport rates are accurately predicted by the gel-on-brush model of the mucociliary apparatus from the relative osmotic moduli of the mucus and periciliary-glycocalyceal (PCL-G) layers. The fluid available to hydrate mucus is generated by transepithelial fluid transport. Feedback interactions between mucus concentrations and cilia beating, via purinergic signaling, coordinate Na+ absorptive vs Cl- secretory rates to maintain mucus hydration in health. In disease, mucus becomes hyperconcentrated (dehydrated). Multiple mechanisms derange the ion transport pathways that normally hydrate mucus in muco-obstructive lung diseases, e.g., CF, COPD, NCFB, and PCD. A key step in muco-obstructive disease pathogenesis is the osmotic compression of the mucus layer onto the airway surface with the formation of adherent mucus plaques and plugs, particularly in distal airways. Mucus plaques create locally hypoxic conditions and produce airflow obstruction, inflammation, infection, and, ultimately, airway wall damage. Therapies to clear adherent mucus with hydrating and mucolytic agents are rational, and strategies to develop these agents are reviewed.

Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model

Mucus clearance, a primary innate defense mechanism of airways, is defective in patients with cystic fibrosis (CF) and CF animals. In previous work, the combination of a low dose of the cholinergic agonist, carbachol with forskolin or a β adrenergic agonist, isoproterenol synergistically increased mucociliary clearance velocity (MCCV) in ferret tracheas. Importantly, the present study shows that synergistic MCCV can also be produced in CF ferrets, with increases ~ 55% of WT. Synergistic MCCV was also produced in pigs. The combined agonists increased MCCV by increasing surface fluid via multiple mechanisms: increased fluid secretion from submucosal glands, increased anion secretion across surface epithelia and decreased Na+ absorption. To avoid bronchoconstriction, the cAMP agonist was applied 30 min before carbachol. This approach to increasing mucus clearance warrants testing for safety and efficacy in humans as a potential therapeutic for muco-obstructive diseases.

Thermal analysis of airway mucus clearance by ciliary activity in the presence of inertial forces

In this study heat transfer effects on cilia induced mucus flow in human airways is presented. The elliptic wave pattern of cilia tips produces metachronal wave which enables the transportation of highly viscous mucus with nonzero inertial forces. Upper Convective Maxwell model is considered as mucus. The governing partial differential equations are transformed from the fixed frame to the wave frame by using Galilean transformation and viscous dissipation is also incorporated in the energy equation. The non-linear governing equations are evaluated by the perturbation technique by using software “MATHEMATICA” and pressure rise is computed by numerical integration. The impact of interested parameters on temperature profile, velocity, pressure rise and pressure gradient are plotted by the graphs. The comparison of velocities due to symplectic and antiplectic metachronal wave are also achieved graphically.

What’s new in airway secretions clearance for adults? A systematic review

Introduction. Airway clearance techniques are an essential part of routine respiratory physiotherapy, enabling bronchial secretion clearance—the mucus overproduction and retaining results in lung function deterioration and disrupts effective pulmonary rehabilitation. Several mucus clearance methods are included in the physiotherapy daily routine of patients with chronic lung conditions; nevertheless, new techniques and approaches are continuously developed. Aim. Thus, this systematic review summarizes novel airway clearance techniques applied in patients with chronic pulmonary conditions. Material and methods. The PubMed, Cochrane Library, and PEDro databases were searched from 2010 to 2021, and studies were selected based on eligibility criteria. Analysis of the literature. 101 patients from five studies describing four different techniques were included. Novel techniques were non-invasive ventilation, intrapulmonary percussive ventilation, trachea vibration, and PEP-sound wave combination. Significant improvements were noted for ventilation homogeneity (NIV), saturation (NIV), respiratory rate (IPV), and diffusion capacity (VL), whereas cardiovascular function and exercise endurance did not change significantly. Conclusion. The presented methods are considered to have similar effectiveness as well-known airway clearance techniques. However, the systematic use of presented methods in routine pulmonary rehabilitation must be preceded by in-depth investigation to provide no-bias results.

Novel therapeutic approaches for the management of cystic fibrosis

Cystic fibrosis (CF) is a genetic condition characterised by the build-up of thick, sticky mucus that can damage many of the body’s organs. It is a life-long disease that results in a shortened life expectancy, often due to the progression of advanced lung disease. Treatment has previously targeted the downstream symptoms such as diminished mucus clearance and recurrent infection. More recently, significant advances have been made in treating the cause of the disease by targeting the faulty gene responsible. Hope for the development of potential therapies lies with ongoing research into new pharmacological agents and gene therapy. This review gives an overview of CF, and summarises the current evidence regarding the disease management and upcoming strategies aimed at treating or potentially curing this condition.

Effect of Non-Newtonian Dynamics on the Clearance of Mucus From Bifurcating Lung Airway Models

Mucus hypersecretion is a common pathophysiological manifestation of several obstructive airway diseases in which the mucociliary clearance is impaired, and the airflow generated by a cough or a forced expiratory maneuver called the huff is primarily responsible for clearing mucus. This airflow driven clearance of mucus is a complex process that is affected by the mucus rheology, airflow rate, airway geometry, and gravity. This study examines the role of mucus rheology in the transport and distribution of mucus in idealized 3D airway geometries. The complex air-mucus interface was tracked by the volume-of-fluid (VOF) model, and the turbulence in the core airflow was modeled using the k–ω shear stress transport (SST) model. Mucus was modeled as a shear-thinning liquid by using a power-law model. The computational model was validated using in vitro experimental data available in the literature. Gravity-dominated eccentric core-annular flow was observed with the core biased toward the outer wall in the inclined daughter branches of the bifurcation models, which transitions into concentric core-annular flow in the trachea. The increase in tangential shear at the interface due to the secondary flow structures developed in the flow divider location resulted in a region of enhanced mucus clearance with reduced mucus layer thickness. Secondary flow developed due to the curvature in the airway geometry resulted in a local redistribution of mucus that reduced the eccentricity. The accumulation of mucus around the carinal ridges and the regions with reduced clearance are sites with the potential for microbial growth.

Update on pharmacotherapy for adult bronchiectasis

Bronchiectasis refers to abnormal dilatation of the bronchi, which leads to the failure of mucus clearance and increased risk of infection. Pharmacotherapy for stable bronchiectasis includes oral or inhaled mucoactive agents, anti-inflammatory therapy, inhaled bronchodilators, long-term antibiotics, and long-term macrolide treatment. Among them, mucoactive agents are the most common adjunctive agents to airway clearance techniques. When patients with impaired lung function suffer from dyspnea, inhaled bronchodilators may be prescribed to relieve the symptom. Long-term macrolide treatment has been proven to prevent exacerbation in patients with frequent bronchiectasis exacerbation. If exacerbation occurs despite the above mentioned treatments, one or two weeks of antibiotics should be prescribed to cover respiratory bacteria that include <i>Pseudomonas aeruginosa</i>. Because evidence supporting the use of pharmacotherapy for bronchiectasis is weak, further research is warranted.