Respiratory Mucus from Asymptomatic Smokers Is Better Hydrated and More Easily Cleared by Mucociliary Action

Rubin, Bruce K.; Ramírez, Óscar; Zayas, J. Gustavo; Finegan, Barry A.; King, Malcolm

doi:10.1164/ajrccm/145.3.545

Cited by 42 publications

(33 citation statements)

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“…CS is highly oxidizing, which decreases CFTR gene expression, and CS exposure also causes CFTR clearance from the plasma membrane into aggresome-like compartments (14,16). Both of these effects result in a functional decrease in CFTR activity in the plasma membrane, which reduces salt and water secretion into the ASL in the face of mucin hypersecretion, causing ASL/mucus dehydration and reduced mucus clearance, thus leading to impaired innate defense (14,17). However, as with many aspects of tobacco exposure, the cell biology underlying CFTR's inhibition following tobacco exposure is likely to be complex, and the underlying mechanisms are currently unknown.…”

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confidence: 99%

Cigarette Smoke-induced Ca2+ Release Leads to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Dysfunction

Rasmussen

Sheridan

Polk

et al. 2014

Journal of Biological Chemistry

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Background: COPD is the 4th leading cause of death worldwide, yet little is known about its pathogenesis. Results: Exposure to cigarette smoke elevated intracellular Ca 2ϩ levels, which triggered CFTR internalization/inhibition. Conclusion: Cigarette smoke-induced Ca 2ϩ release and CFTR inhibition may be involved in COPD pathogenesis. Significance: Our data provide novel information regarding the underlying mechanism of cigarette smoke-induced lung injury.

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confidence: 99%

Cigarette Smoke-induced Ca2+ Release Leads to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Dysfunction

Rasmussen

Sheridan

Polk

et al. 2014

Journal of Biological Chemistry

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“…The prolonged decrease in galactose content in dogs exposed was interpreted as a change in the nature of the mucus. In humans, we previously demonstrated an almost identical pattern regarding a fall in mucus rigidity with an eventual return to normal values (4,7). It is tempting to assume that a similar biochemical change in mucus composition might have happened in these subjects as well.…”

Section: Discussionmentioning

confidence: 74%

“…any studies have shown that smoking leads to abnormalities in mucus clearance, both in humans (1)(2)(3)(4) and in animals (5). We have demonstrated that canine mucus rheology is altered by cigarette smoke exposure, initially in a way that predictive equations suggest would increase mucociliary transportability (6).…”

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confidence: 77%

“…In two previous studies, we collected and analyzed tracheal mucus collected on a bronchoscopy brush from patients undergoing diagnostic bronchoscopy (7), or from the endotracheal tube of patients without signs or symptoms of lung disease who required elective nonpulmonary surgery (4). In both of these studies, symptom-free early tobacco smokers with 10 or fewer pack-years of smoking history had mucus that was less rigid and more easily cleared by cilia.…”

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confidence: 99%

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Bronchial Mucus Properties in Lung Cancer: Relationship with Site of Lesion

et al. 1999

Canadian Respiratory Journal

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OBJECTIVE: To compare the biophysical properties of mucus from the left and right mainstem bronchi in patients undergoing diagnostic bronchoscopy because of a unilateral radiological abnormality. It was hypothesized that abnormalities in the properties of mucus would be greater on the side with the lesion and that this would be most obvious in patients with unilateral lung cancer.PATIENTS AND METHODS: Bilateral paired samples of bronchial mucus were taken from 38 nonatopic patients (aged 59.8±12.6 years) including 16 nonsmokers, 14 current smokers and eight exsmokers (more than one year). Twenty of the 38 patients had a radiologically defined unilateral abnormality. Eight of these 20, including one nonsmoker, had lung cancer. The viscoelastic properties of the collected mucus were determined by magnetic microrheometry, and the analysis was carried out without knowledge of the histological diagnosis or source.RESULTS: The rheological properties of mucus strongly suggested which was the abnormal side. Within the group of 20 patients with a unilateral radiological abnormality, mucus from the side of the lesion had a lower value of the loss tangent, tan δ100 (P=0.004), indicating greater mucus recoil. This is consistent with poor mucus cough clearability on the lesion side. All eight cancer patients fit this mucus rheological pattern with a lower value of tan δ100 on the affected side (P=0.007). Four of the five other patients with a similar mucus abnormality were categorized as high cancer risk by other criteria, while six of seven patients with mucus that did not have this abnormality were considered to be lower risk. Based on the mucus analysis done at the time of the bronchoscopy, two of the ‘noncancer’ patients initially designated as high risk had cancer detected after several months of follow-up. Only two of the 18 patients without a defined unilateral lesion fit the mucus ‘cancer pattern’.CONCLUSIONS: These findings are consistent with the hypothesis that either abnormalities in mucus properties may represent a risk factor for the development of lung cancer or that bronchial mucus abnormalities may be associated with products secreted by the tumours that, in turn, may suppress mucus clearance.

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“…We found, for example, that respiratory mucus from asymptomatic smokers is better hydrated and more easily cleared by mucociliary action than mucus from nonsmokers [60]. However, this apparent "advantage" to smoking disappears with continued exposure, over the course of 20-40 pack-years, and abnormalities in the elastic recoil of mucus predictive of poor cough clearance eventually develop [61].…”

Section: Large Animal Models For Mucus Hypersecretionmentioning

confidence: 73%

Experimental models for studying mucociliary clearance

King¹

1998

Eur Respir J

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Respiratory tract mucus is a viscoelastic gel, the rheological properties of which are determined mainly by its content of mucous glycoproteins and water. The rheology and quantity of mucus, in concert with ciliary factors, are the major determinants of mucociliary clearance.A wide range of animal models for studying the secretion and clearance of mucus are available. Ex vivo models, such as the frog palate or excised bovine trachea, provide direct, meaningful data regarding the clearability of mucus. Rodent models of chronic bronchitis, based on irritant gas or cigarette smoke exposure, show important features of the human condition in a relatively short time. The rheological characterization of mucus is made difficult by the small quantities obtainable, particularly from normal animals.Large animal models, such as the dog or sheep, although more expensive, offer many advantages, such as the ability to carry out long-term serial measurements, and to make integrated measurements of the clearance of mucus, ciliary function, epithelial ion transport, and the rheology of mucus in the same preparation. Eur Respir J 1998; 11: 222-228 The viscoelastic properties of mucusDue to the cross-linking of glycoproteins, the rheological behaviour of mucus is described as viscoelastic, having characteristics of both a liquid and a solid [1,2]. Viscosity is the resistance to flow, and represents the capacity of a material to absorb energy as it moves. Elasticity is the capacity of a material to store the energy used to move or deform it. With ideal fluids, viscosity is independent of the stress applied. With viscoelastic liquids, such as mucus, viscosity decreases with increasing stress or rate of strain (shear rate). Mucus responds to stress with an initial solid-like deformation, followed by a viscoelastic deformation and finally by a period of steady flow, in which the rate of deformation is constant. Only partial recovery of the strain follows removal of the stress, indicating a permanent deformation of its gel structure. Changes in the viscosity and elasticity of mucus are generally interrelated.Mucus exhibits shear-thinning following exposure to high shear forces, exhibiting a decreased viscosity at low shear rates. Some shear-thinning may be permanent, indicating altered molecular structure, whilst some shearthinning, termed "thixotropy", may be reversible.The viscoelasticity of mucus can be effectively described by two relatively independent quantities, G* and tangent (tan) δ, which vary with measurement frequency. The mechanical impedance (G*), is the vector sum of viscosity and elasticity; it can be termed the "rigidity factor". Tan δ is the ratio of viscosity to elasticity; it is also known as the loss tangent and can be considered as a "recoil factor". The relative proportions of elasticity and viscosity are important in describing how a material, such as mucus, behaves when it is subjected to external forces. Rheological assessment of mucus Collection of mucusTracheal mucus can be collected by a modificat...

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Respiratory Mucus from Asymptomatic Smokers Is Better Hydrated and More Easily Cleared by Mucociliary Action

Cited by 42 publications

References 4 publications

Cigarette Smoke-induced Ca2+ Release Leads to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Dysfunction

Cigarette Smoke-induced Ca2+ Release Leads to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Dysfunction

Bronchial Mucus Properties in Lung Cancer: Relationship with Site of Lesion

Experimental models for studying mucociliary clearance

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