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Key Event Title
Mucociliary Clearance, Decreased
|Level of Biological Organization|
Key Event Components
|mucociliary clearance trait||decreased|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Oxidative stress Leading to Decreased Lung Function||KeyEvent||Karsta Luettich (send email)||Open for comment. Do not cite|
|Ox stress-mediated CFTR/ASL/CBF/MCC impairment||KeyEvent||Karsta Luettich (send email)||Open for comment. Do not cite|
|ox stress-mediated FOXJ1/cilia/CBF/MCC impairment||KeyEvent||Karsta Luettich (send email)||Open for comment. Do not cite|
|Homo sapiens||Homo sapiens||High||NCBI|
|Sus scrofa domesticus||Sus scrofa domesticus||Moderate||NCBI|
|Ovis aries||Ovis aries||Moderate||NCBI|
|Cavia porcellus||Cavia porcellus||Moderate||NCBI|
|Canis lupus||Canis lupus||Moderate||NCBI|
|Rana catesbeiana||Rana catesbeiana||Moderate||NCBI|
|Oryctolagus cuniculus||Oryctolagus cuniculus||Moderate||NCBI|
|All life stages||High|
Key Event Description
In healthy adults, tracheal mucus movement varies from 4 to >20 mm/min (Stannard and O'Callaghan, 2006), whereas mucociliary clearance (MCC) in the small airways is slower due to the lower number of ciliated cells (fewer cilia) and their shorter length (Foster et al., 1980; Iravani, 1969; Wanner et al., 1996). Since optimal MCC is dependent in multiple factors, including cilia number and structure as well as ASL and mucus properties, any disturbances of these can lead to impaired MCC. While high humidity or infection can enhance MCC, long-term exposure to noxious substances (e.g. cigarette smoke) lead to decreased mucus clearance from the airways. In most instances this is reflected by decreased mucus transport rates or velocities.
How It Is Measured or Detected
In humans, MCC has been assessed traditionally following inhalation of radio-labeled particles such as 99Tcm-labeled polystyrene particles, resin particles or serum albumin and following their clearance at regular intervals by radioimaging using gamma cameras (Agnew et al., 1986; Kärjä et al., 1982). Taking into account inhalation volumes and flow rates, lung airflow, particle deposition and retention, clearance rates can be calculated and effects of e.g. drugs on MCC can be examined. Alternatively, since MCC occurs at a similar rate in the nose to that in trachea and bronchi (Andersen and Proctor, 1983; Rutland and Cole, 1981) and for ease of use, measurements of MCC can be restricted to that of nasal MCC only. Probably one of the simplest methods is the saccharin transit test (STT). For this test, a small particle of saccharin is placed behind the anterior end of the inferior turbinate. The saccharin will be transported by mucociliary action toward the nasopharynx, where its sweet taste is perceived. When MCC is impaired, saccharin transit times will increase, with a 10- to 20-minute delay being considered a clinical sign of decreased MCC. Using the same principle, the test can also be performed or complemented with dyes such as indigo carmine or methylene blue (Deborah and Prathibha, 2014).
In experimental animals, MCC has been evaluated by gamma-scintigraphy (Greiff et al., 1990; Hua et al., 2010; Read et al., 1992), fluorescence videography/fluoroscopy (in explanted tracheas etc.) (Grubb et al., 2016; Rogers et al., 2018), or by 3D-SPECT (Ortiz Belda et al., 2016). Direct observation of particle movement across airway epithelia to determine mucus velocity or transport rates by using a fiberoptic bronchoscope may be helpful when working in larger animals such as dogs (King, 1998). In vitro, freshly excised frog palate preparations have been used to assess cilia function and mucociliary transport by videomicroscopy (Macchione et al., 1995; Macchione et al., 1999; Trindade et al., 2007). Murine and human nasal, bronchial and small airway epithelial models grown at the air-liquid interface are also suitable in vitro test systems for determining mucus transport by tracing inert particle movement with a set-up similar to that used for assessing CBF (Benam et al., 2018; Fliegauf et al., 2013; Knowles and Boucher, 2002; Sears et al., 2015).
Domain of Applicability
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