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Event: 943

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Hypersecretion, Mucus

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Hypersecretion, Mucus
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
mouse Mus musculus High NCBI
rat Rattus norvegicus High NCBI
human Homo sapiens High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Mucus hypersecretion occurs in obstructive airway diseases such as COPD, asthma, and cystic fibrosis. Excessive mucus is produced and plugging of airways can occur in small airways, leading to breathing difficulty. Mucins are produced in response to irritants such as virus, bacteria and environmental particulates including cigarette smoke, stimulating coughing to assist clearance of mucus (Nadel, 2013).

In large airways, cough receptors and submucosal gland ducts are co-localized, assisting the clearance of mucus via coughing, and stimulation of vagal sensory nerves cause reflex smooth muscle contraction, contributing to airway narrowing. In small airways, early detection is limited since they do not contain cough receptors and airway resistance due to obstruction is not noticeably changed because there are many small airways (Nadel, 2013).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible?

In vivo

Studies investigate mucus hypersecretion in animals in response to a stimulant for a number of weeks, measuring increased cellular rate of glycoprotein secretion after 6 weeks of sulfur dioxide exposure (Coles et al., 1979), increased number of mucous glycoproteins (140-535%) by AB-PAS staining after 4 weeks of ovalbumin exposure (Shore et al., 1995). Shorter term experiments with less dramatic increases in mucus increase are also described as mucus hypersecretion, for example 15% increase in mucus production shown by AB-PAS staining after three weeks of acrolein exposure (Liu et al., 2009).

Since there is no clear quantitative cutoff for mucus hypersecretion, studies sometimes use the term loosely equating mucus hypersecretion with an increase in mucus production compared to normal over a short time period. Measures include mucin released into tracheobronchial lavage fluid by a MUC5AC-specific ELISA after 72 hours OVA challenge (Singer et al., 2004) or increased Muc5ac RNA and protein expression after 4 days of LPS in rats (Ou et al., 2008).


Mucus hypersecretion is detected by continuous phlegm production for a number of weeks in the absence of chest infection, assessed by either questioning the patient (routine procedure) or measuring sputum volume, which is performed less frequently. In the Copenhagen City Heart Study, chronic mucus hypersecretion was considered present when cough and sputum had lasted at least 3 months for more than 1 year (Vestbo et al., 1996).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Many studies in mouse, rat and human describe the occurrence of mucus hypersecretion due to various stimuli. Studies in humans define mucus hypersecretion functionally, while studies in rats and mice define mucus hypersecretion as an increase in mucus production with no clear quantitative cutoff for amount and duration.


List of the literature that was cited for this KE description. More help

1. Coles, S.J., Levine, L.R., and Reid, L. (1979). Hypersecretion of mucus glycoproteins in rat airways induced by tobacco smoke. Am. J. Pathol. 94, 459–471.

2. Hewson, C., Edbrooke, M., and Johnston, S. (2004). PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-alpha, Ras/Raf, MEK, ERK and Sp1-dependent mechanisms. J Mol Biol 344, 683–695.

3. Liu, D.-S., Wang, T., Han, S.-X., Dong, J.-J., Liao, Z.-L., He, G.-M., Chen, L., Chen, Y.-J., Xu, D., Hou, Y., et al. (2009). p38 MAPK and MMP-9 cooperatively regulate mucus overproduction in mice exposed to acrolein fog. Int. Immunopharmacol. 9, 1228–1235.

4. Nadel, J. (2013). Mucous hypersecretion and relationship to cough. Pulm Pharmacol Ther 26, 510–513.

5. Ou, X.-M., Wang, B.-D., Wen, F.-Q., Feng, Y.-L., Huang, X.-Y., and Xiao, J. (2008). Simvastatin attenuates lipopolysaccharide-induced airway mucus hypersecretion in rats. Chin. Med. J. (Engl.) 121, 1680–1687.

6. Shore, S., Kobzik, L., Long, N., Skornik, W., Van Staden, C., Boulet, L., Rodger, I., and Pon, D. (1995). Increased airway responsiveness to inhaled methacholine in a rat model of chronic bronchitis. Am J Respir Crit Care Med 151, 1931–1938.

7. Singer, M., Martin, L.D., Vargaftig, B.B., Park, J., Gruber, A.D., Li, Y., and Adler, K.B. (2004). A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nat. Med. 10, 193–196.

8. Vestbo, J., Prescott, E., and Lange, P. (1996). Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group. Am J Respir Crit Care Med 153, 1530–1535.