A Brief History of Bronchitis in England and Wales.

Chronic bronchitis is associated with hypertrophy of airway submucosal glands and with mucus and squamous metaplasia of the surface epithelium. A historical review of research on these and other pathological changes is provided. Next, from annual reports of the Registrar-General's Office (and later the Office of National Statistics), death rates per unit population from acute and chronic bronchitis (a term that here includes chronic obstructive pulmonary disease [COPD]) are calculated for England and Wales from 1838 to the present.

Why Airway Gland Secretions Are Abnormally Sticky in Cystic Fibrosis, and Why Not Much Can Be Done About It.

In this issue of Developmental Cell, Xie et al. show that in cystic fibrosis, airway gland mucus gels form under conditions of high acidity and protein concentration. This causes them to be unusually stiff.

Early studies on the surface epithelium of mammalian airways.

This article traces the beginnings of the various areas of physiological research on airway epithelium. First mentioned in 1600, it was not until 1834 that it was found to be ciliated. Goblet and basal cells were described in 1852, to be followed by ~10 other epithelial cell types (the most recent in 2018).

Early studies of airway submucosal glands.

This historical article provides a comprehensive review of early research on the structure and function of airway submucosal glands. The literature before 1950 or so, is virtually unknown, but in addition to being of historical interest it contains much of relevance to current research. Airway glands were first mentioned in 1602.

Airway Gland Structure and Function.

Submucosal glands contribute to airway surface liquid (ASL), a film that protects all airway surfaces. Glandular mucus comprises electrolytes, water, the gel-forming mucin MUC5B, and hundreds of different proteins with diverse protective functions. Gland volume per unit area of mucosal surface correlates positively with impaction rate of inhaled particles.

Distribution and size of mucous glands in the ferret tracheobronchial tree.

A transgenic ferret model of cystic fibrosis has recently been generated. It is probable that malfunction of airway mucous glands contributes significantly to the airway pathology of this disease. The usefulness of the ferret model may therefore depend in part on how closely the airway glands of ferrets resemble those of humans.

A simple device to illustrate the Einthoven triangle.

The Einthoven triangle is central to the field of electrocardiography, but the concept of cardiac vectors is often a difficult notion for students to grasp. To illustrate this principle, we constructed a device that recreates the conditions of an ECG reading using a battery to simulate the electrical vector of the heart and three voltmeters for the main electrocardiographic leads. Requiring minimal construction with low cost, this device provides hands-on practice that enables students to rediscover the principles of the Einthoven triangle, namely, that the direction of the cardiac dipole can be predicted from the deflections in any two leads and that lead I + lead III = lead II independent of the position of heart's electrical vector.

Differential effects of extracellular ATP on chloride transport in cortical collecting duct cells.

Extracellular ATP in the cortical collecting duct can inhibit epithelial sodium channels (ENaC) but also stimulate calcium-activated chloride channels (CACC). The relationship between ATP-mediated regulation of ENaC and CACC activity in cortical collecting duct cells has not been clearly defined. We used the mpkCCD(c14) cortical collecting duct cell line to determine effects of ATP on sodium (Na(+)) and chloride (Cl(-)) transport with an Ussing chamber system.

Cystic fibrosis and the relationship between mucin and chloride secretion by cultures of human airway gland mucous cells.

We investigated how cystic fibrosis (CF) alters the relationship between Cl(-) and mucin secretion in cultures of non-CF and CF human tracheobronchial gland mucous (HTGM and CFTGM, respectively) cells. Biochemical studies showed that HTMG cells secreted typical airway mucins, and immunohistochemical studies showed that these cells expressed MUC1, MUC4, MUC5B, MUC8, MUC13, MUC16, and MUC20. Effects of cumulative doses of methacholine (MCh), phenylephrine (Phe), isoproterenol (Iso), and ATP on mucin and Cl(-) secretion were studied on HTGM and CFTGM cultures.

Quantitative real-time PCR for rhinovirus, and its use in determining the relationship between TCID50 and the number of viral particles.

The development of a quantitative real-time PCR (qPCR) assay for human rhinovirus serotype 16 (HRV16) is described using the plasmid pR16.11, which contains the full-length genome of HRV16. A standard curve was generated by plotting the critical threshold (C(t)) against numbers of plasmid.

Transgenic animals may help resolve a sticky situation in cystic fibrosis.

Cystic fibrosis (CF) is caused by defects in the CFTR, a cAMP-activated Cl- channel of epithelia. The resulting reduction in epithelial fluid transport creates abnormally viscous secretions from airway mucous glands that may be a major factor in CF pathology. Mouse airways have few mucous glands, and the mouse model of CF exhibits no significant airway disease.

CFTR and calcium-activated chloride channels in primary cultures of human airway gland cells of serous or mucous phenotype.

Using cell culture models, we have investigated the relative importance of cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCC) in Cl secretion by mucous and serous cells of human airway glands. In transepithelial recordings in Ussing chambers, the CFTR inhibitor CFTR(inh)-172 abolished 60% of baseline Cl secretion in serous cells and 70% in mucous. Flufenamic acid (FFA), an inhibitor of CaCC, reduced baseline Cl secretion by ∼20% in both cell types.

Interleukin-13-induced mucous metaplasia increases susceptibility of human airway epithelium to rhinovirus infection.

Infection of airway epithelium by rhinovirus is the most common cause of asthma exacerbations. Even in mild asthma, airway epithelium exhibits mucous metaplasia, which increases with increasing severity of the disease. We previously showed that squamous cultures of human airway epithelium manifest rhinoviral infection at levels many times higher than in well-differentiated cultures of a mucociliary phenotype.

Cultures of human tracheal gland cells of mucous or serous phenotype.

There are two main epithelial cell types in the secretory tubules of mammalian glands: serous and mucous. The former is believed to secrete predominantly water and antimicrobials, the latter mucins. Primary cultures of human airway gland epithelium have been available for almost 20 yr, but they are poorly differentiated and lack clear features of either serous or mucous cells.

In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects.

Background: Human rhinoviruses (HRVs) characteristically cause upper respiratory tract infection, but they also infect the lower airways, causing acute bronchitis and exacerbating asthma.

Objective: Our purpose was to study ex vivo the differences in the response to HRV infection of nasal and bronchial epithelial cultures from the same healthy and asthmatic individuals using conditions favoring development of fully differentiated, pseudostratified mucociliary epithelium.

Methods: Cells from the inferior turbinates and bronchial tree of 5 healthy and 6 asthmatic individuals were cultured at an air-liquid interface.

Basolateral Cl channels in primary airway epithelial cultures.

Salt and water absorption and secretion across the airway epithelium are important for maintaining the thin film of liquid lining the surface of the airway epithelium. Movement of Cl across the apical membrane involves the CFTR Cl channel; however, conductive pathways for Cl movement across the basolateral membrane have been little studied. Here, we determined the regulation and single-channel properties of the Cl conductance (G(Cl)) in airway surface epithelia using epithelial cultures from human or bovine trachea and freshly isolated ciliated cells from the human nasal epithelium.

Mechanisms of acid and base secretion by the airway epithelium.

One of the main functions of the airway epithelium is to inactivate and remove infectious particles from inhaled air and thereby prevent infection of the distal lung. This function is achieved by mucociliary and cough clearance and by antimicrobial factors present in the airway surface liquid (ASL). There are indications that airway defenses are affected by the pH of the ASL and historically, acidification of the airway surfaces has been suggested as a measure of airway disease.

Innate immune responses of human tracheal epithelium to Pseudomonas aeruginosa flagellin, TNF-alpha, and IL-1beta.

We measured innate immune responses by primary human tracheal epithelial (HTE) cells grown as confluent, pseudostratified layers during exposure to inflammatory activators on apical vs. basolateral surfaces. Apical Pseudomonas aeruginosa strain PAK (but not flagellin mutant PAK.

Are Drosophila a useful model for understanding the toxicity of inhaled oxidative pollutants: a review.

Oxidative atmospheric pollutants represent a significant stress and cause injury to both vertebrate and invertebrate species. In both, the biosurfaces of their respiratory apparatus are directly exposed to oxidizing pollutant-induced stresses. Respiratory-tract surfaces contain integrated antioxidant systems that appear to provide a primary defense against environmental insults caused by inhaled atmospheric reactive oxygen species (ROS) and reactive nitrogen species (RNS), whether gaseous or particulate.

Expansion of cultures of human tracheal epithelium with maintenance of differentiated structure and function.

We have developed a technique for expanding primary cultures of human tracheal epithelium while minimizing loss of differentiated structure and function. Cells were seeded at 2 x 10(4) cells/cm2 into T75 flasks and trypsinized when approximately 80% confluent. The dispersed cells were then passaged at the same plating density into further T75 flasks or seeded at 5 x 10(5) cells/cm2 on porous-bottomed inserts and maintained with an air-interface.

A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells.

An oligomeric proanthocyanidin (SP-303) extracted from the bark latex of the tree Croton lechleri (family Euphorbiaceae) is a potent inhibitor of cholera toxin-induced fluid accumulation and chloride secretion. The manufacturing process for SP-303 was optimized and simplified to produce an increased yield of the herbal extract. The novel extract (named SB-300) contained on average 70.

Endotoxin induces leukocyte transmigration and changes in permeability of the airway epithelium via protein-kinase C and extracellular regulated kinase activation.

Lipopolysaccharide (LPS) endotoxin of Gram-negative bacteria compromises the integrity of the airway epithelial barrier and initiates migration of leukocytes across the epithelium. The goal of the present study was to identify the role of extracellular regulated kinase (ERK1/2) transduction pathways in these processes. The first aim was to determine whether LPS induces ERK1/2 activation and changes in epithelial permeability in epithelial cells alone or only in the presence of immune cells.

Polarized cultures of human airway epithelium from nasal scrapings and bronchial brushings.

Airway epithelial cultures are generally derived from tracheas postmortem or from surgical specimens of nasal polyps or turbinates. Scrapings of the mucosal surface have been little used as starting material for cultures because of their low yield of epithelial cells and their contamination with mucous secretions, blood, and underlying connective tissue. For the first time, we report that human airway epithelial cells obtained from nasal scrapings or bronchial brushings can be grown in culture to produce polarized cell sheets suitable for studies of vectorial transport.

Activation of extracellular regulated kinases is required for the increase in airway epithelial permeability during leukocyte transmigration.

The goal of this study was to determine whether the extracellular regulated kinases (ERK1/2) are involved in leukocyte transmigration across airway epithelium and the associated changes in epithelial permeability. In vitro, we used formyl-methionyl-leucyl-phenylalanine (fMLP) to induce migration of HL-60 cells (a human leukocyte cell line) across sheets of polarized Calu-3 airway epithelial cells and also to induce migration of human neutrophils across primary cultures of cow tracheal epithelial cells. In both systems, leukocyte migration decreased transepithelial electrical resistance (R(te)), increased epithelial permeability to albumin (P(alb)), and increased ERK1/2 phosphorylation in epithelial cells.

Measurement of nasal potential difference in mild asthmatics.

Study Objective: To determine whether ion transport or barrier function across the nasal epithelium are altered in asthmatics.

Design: In this pilot study, the nasal potential difference (PD) was measured using the technique established by Knowles and colleagues. A flowing agar bridge made electrical contact with the surface of the nasal epithelium along the floor of the nose.