Airway hydration and COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the prevalent causes of worldwide mortality and encompasses two major clinical phenotypes, i.e., chronic bronchitis (CB) and emphysema. The most common cause of COPD is chronic tobacco inhalation. Research focused on the chronic bronchitic phenotype of COPD has identified several pathological processes that drive disease initiation and progression. For example, the lung’s mucociliary clearance (MCC) system performs the critical task of clearing inhaled pathogens and toxic materials from the lung. MCC efficiency is dependent on: (i) the ability of apical plasma membrane ion channels such as the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na+ channel (ENaC) to maintain airway hydration; (ii) ciliary beating; and, (iii) appropriate rates of mucin secretion. Each of these components is impaired in CB and likely contributes to the mucus stasis/accumulation seen in CB patients. This review highlights the cellular components responsible for maintaining MCC and how this process is disrupted following tobacco exposure and with CB. We shall also discuss existing therapeutic strategies for the treatment of chronic bronchitis and how components of the MCC can be used as biomarkers for the evaluation of tobacco or tobacco-like-product exposure.

Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis

“…The data are summarized in Fig. 2B, showing similar micromolar drug concentration causing 50% inhibition (IC 50 ) values for inhibition of Cl 2 /SCN 2 , Cl 2 /I 2 , and Cl 2 /NO 3 2 exchange by both compounds. The kinetics of PDS inh -A01 and PDS inh -C01 action were measured for Cl 2 /SCN 2 exchange using inhibitors at 10 mM, a concentration producing partial inhibition (Fig.…”

“…In the thyroid pendrin is expressed on the apical membrane of follicular cells, where it facilitates I 2 efflux into the follicle colloid for thyroid hormone synthesis (2,15). In the kidney pendrin is expressed in the apical plasma membrane of type B and non-A/non-B intercalated cells, where it facilitates Cl 2 absorption and HCO 3 2 secretion, ABBREVIATIONS: ASL, airway surface liquid; CaCC, calcium-activated chloride channel; CF, cystic fibrosis; CFBE, human cystic fibrosis bronchial epithelial; CFTR, cystic fibrosis transmembrane conductance regulator; ENaC, epithelial sodium channel; EYFP-HIF, enhanced yellow fluorescent protein-H148Q/I152L/F46L; FRT, Fischer rat thyroid; HBE, human bronchial epithelial; IC 50 , drug concentration causing 50% inhibition; I sc , short-circuit current; PCL, periciliary layer; UCSF, University of California, San Francisco; YFP, yellow fluorescent protein although kidney abnormalities are rare in Pendred syndrome (4,6,16).…”

Will chronic e-cigarette use cause lung disease?

“…It is thought that ϳ85% of all lung cancer is caused by smoking, and secondhand smoke exposure increases the chance of lung cancer by ϳ25% (27). COPD is also caused primarily by tobacco exposure in Western countries and kills a similar amount of people as lung cancer (ϳ140,000/yr) (12,60). COPD is also the third leading cause of death in the USA and worldwide (157), although tobacco exposure is a primary risk factor of COPD in first-world countries; smoke from biomass fuels is also a risk factor for COPD in second-and third-world countries (49).…”

Carvedilol binding to β2-adrenergic receptors inhibits CFTR-dependent anion secretion in airway epithelial cells

“…The decrease in secretion was found to be due to rapid internalization of CFTR, which involved trafficking from the plasma membrane to a low-solubility, perinuclear compartment without lysosomal degradation (9). Internalization was also dependent on CSEinduced activation of the ERK/MAPK pathway, and treatment with N-acetylcysteine was shown to block the increase in ERK phosphorylation, suggesting a role for oxidative stress in downregulation of CFTR (12,43). The results of the present study and the study of Zhou et al (44) described above suggest an additional possibility linked to the activation of ␤ 2 -ARs and ␤-arrestin signaling that may also contribute to smokinginduced CFTR internalization and subsequent dehydration of airway surface liquid.…”

“…Acute and chronic cigarette exposure is also known to cause rapid and sustained inhibition of CFTR-dependent anion secretion in vitro and in vivo (7)(8)(9)(10)12). The decrease in secretion was found to be due to rapid internalization of CFTR, which involved trafficking from the plasma membrane to a low-solubility, perinuclear compartment without lysosomal degradation (9).…”