Mucus Structure, Viscoelastic Properties, and Composition in Chronic Respiratory Diseases

Abstract

The respiratory mucus, a viscoelastic gel, effectuates a primary line of the airway defense when operated by the mucociliary clearance. In chronic respiratory diseases (CRDs), such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), the mucus is overproduced and its solid content augments, changing its structure and viscoelastic properties and determining a derangement of essential defense mechanisms against opportunistic microbial (virus and bacteria) pathogens. This ensues in damaging of the airways, leading to a vicious cycle of obstruction and infection responsible for the harsh clinical evolution of these CRDs. Here, we review the essential features of normal and pathological mucus (i.e., sputum in CF, COPD, and asthma), i.e., mucin content, structure (mesh size), micro/macro-rheology, pH, and osmotic pressure, ending with the awareness that sputum biomarkers (mucins, inflammatory proteins and peptides, and metabolites) might serve to indicate acute exacerbation and response to therapies. There are some indications that old and novel treatments may change the structure, viscoelastic properties, and biomarker content of sputum; however, a wealth of work is still needed to embrace these measures as correlates of disease severity in association with (or even as substitutes of) pulmonary functional tests.

CFTR dysfunction leads to defective bacterial eradication on cystic fibrosis airways

“…First, the mucociliary clearance mechanism is constructed by viscoelastic and discontinued mucus ( Rogers et al, 2022 ; Abrami et al, 2024 ) that flow on a watery and gel-like layer, the periciliary layer (PCL) ( Widdicombe and Widdicombe, 1995 ; Button et al, 2012 ) ( Figure 1 ). Sticky mucus traps inhaled bacteria, debris and other particles, while the cilia of epithelial cells in the underlying PCL propel the mucus and trapped substances ( Figure 1 ) towards to the pharynx, where they form the sputum for expectoration ( Bustamante-Marin and Ostrowski, 2017 ; Rogers et al, 2022 ).…”

Cough in non-cystic fibrosis bronchiectasis

“…The ML, rich in mucin, binds to inhaled foreign materials and pathogens. In healthy individuals, this layer comprises approximately 98% water, 0.9% salts, and 1.1% organic content, including 0.5% mucins and 0.6% globular proteins [20]. Both club and goblet cells secrete mucin.…”

“…These mucins prevent mucus and particle penetration into the PCL, which maintains hydration against the osmotically active ML. In addition to their molecular barrier features, cell surface mucins play a substantial role in modulating inflammatory and immune responses [20,25,26]. Furthermore, the PCL allows cilia to beat without being trapped in the ML and acts as a lubricant that enables mucus to slide along the interface [27].…”