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Event: 1251

Key Event Title

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

Chronic, Mucus hypersecretion

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
Chronic, Mucus hypersecretion
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Biological Context

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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
Organ term

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
Process Object Action
mucus secretion lung goblet cell increased

Key Event Overview

AOPs Including This Key Event

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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
human Homo sapiens Moderate NCBI

Life Stages

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Life stage Evidence
Adult Moderate

Sex Applicability

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Term Evidence
Mixed Moderate

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 is a physiological response to inhalation exposures to pollutants or infectious agents. As such, it is typically of short duration and does not pose a major problem to normal lung function. Under chronic stress/exposure conditions, airway remodeling and mucus hypersecretion will cease being a physiological stress response aimed at eliminating the potential hazard and regaining the balance of a healthy airway epithelium, and chronic mucus hypersecretion will ensue. This is the case in many respiratory diseases that feature a chronic inflammatory micoenvironment such as chronic obstructive pulmonary disease and asthma (Evans et al., 2009; Allinson et al., 2016). Recent estimates of chronic mucus hypersecretion in the global population range from 3.5 to 27% (Kim et al. 2011; Martinez et al. 2014; Montes De Oca et al. 2012).

How It Is Measured or Detected

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To our knowledge, there is no report regarding the assessment of chronic mucus hypersecretion in vitro. This is most likely related to the fact that many in vitro studies are of short duration, employing acute exposures to mucus-inducing stimuli. However, mucus hypersecretion is a feature of animal models of asthma (Shim et al., 2001; Singer et al., 2004; Song et al., 2016) and occurs in mice and rats following inhalation of e.g. acrolein and cigarette smoke (Deshmukh et al., 2008; Yang et al., 2012; Chen et al., 2013; Vlahos and Bozinovski, 2015; Liu et al., 2017). There appears to be no consensus as to the "chronicity" of mucus hypersecretion, and no standardized measure exists.

Clinically, coughing and sputum production for >3 months in at least two consecutive years is defined as (chronic) mucus hypersecretion (Vestbo, 2002). More recently, questionnaires such as the St George’s Respiratory Questionnaire (Hardin and Rennard, 2015), the COPD Assessment Test (CAT) (Stott-Miller et al., 2020) and the American Thoracic Society Questionnaire (Cassidy et al., 2015) have been employed to evaluate cough and sputum production, and hence mucus hypersecretion. At times, sputum volumes are recorded as measure of mucus production. Current clinical practice, however, does not include a quantitative measure of mucus hypersecretion.

Domain of Applicability

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

Mucus hypersecretion was described in mice and rats following ovalbumin challenge (Shim et al., 2001; Singer et al., 2004; Song et al., 2016) or exposure to acrolein and cigarette smoke (Deshmukh et al., 2008; Yang et al., 2012; Chen et al., 2013; Vlahos and Bozinovski, 2015; Liu et al., 2017). Chronic mucus hypersecretion is also frequently found in long-term smokers, COPD patients with chronic bronchitis and asthma patients (Danahay and Jackson, 2005).


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

Abbey, D.E., Nishino, N., and McDonnell, W.F. (1998). Development of chronic productive cough as associated with long-term ambient inhalable particulate pollutants (PM10) in nonsmoking adults: the AHSMOG study. Appl. Occup. Environ. Hyg. 13, 444-452.

Allinson, J.P., Hardy, R., Donaldson, G.C., Shaheen, S.O., Kuh, D., and Wedzicha, J.A. (2016). The presence of chronic mucus hypersecretion across adult life in relation to chronic obstructive pulmonary disease development. Am. J. Resp. Crit. Care Med. 193, 662-672.

Cassidy, R.N., Roberts, M.E., and Colby, S.M. (2015). Validation of a Respiratory Symptom Questionnaire in Adolescent Smokers. Tob. Regul. Sci. 1, 121-128. 

Chen, P., Deng, Z., Wang, T., Chen, L., Li, J., Feng, Y., et al. (2013). The potential interaction of MARCKS-related peptide and diltiazem on acrolin-induced airway mucus hypersecretion in rats. Intl. Immunopharmacol. 17, 625-632.

Danahay, H., and Jackson, A.D. (2005). Epithelial mucus-hypersecretion and respiratory disease. Inflamm. Allergy Drug Targets 4, 651-664.

de Oca, M.M., Halbert, R.J., Lopez, M.V., Perez-Padilla, R., Tálamo, C., Moreno, D., et al. (2012). The chronic bronchitis phenotype in subjects with and without COPD: the PLATINO study. Eur. Respir. J. 40(1), 28-36. 

Deshmukh, H.S., Shaver, C., Case, L.M., Dietsch, M., Wesselkamper, S.C., Hardie, W.D., Korfhagen, T.R., Corradi, M., Nadel, J.A., and Borchers, M.T. (2008). Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production. Am. J. Resp. Cell Mol. Biol. 38, 446-454.

Dijkstra, A.E., de Jong, K., Boezen, H.M., Kromhout, H., Vermeulen, R., Groen, H.J.M., et al. (2014). Risk factors for chronic mucus hypersecretion in individuals with and without COPD: influence of smoking and job exposure on CMH. Occup. Environ. Med. 71, 346-352. 
Evans, C. M., Kim, K., Tuvim, M. J., & Dickey, B. F. (2009). Mucus hypersecretion in asthma: causes and effects. Curr. Opin. Pulm. Med. 15, 4–11.
Hardin, M., and Rennard, S.I. (2017). What's New with the St George's Respiratory Questionnaire and Why Do We Care? Chronic Obstr. Pulm. Dis. 4, 83-86. 
Harmsen, Thomsen, S.F., Ingebrigtsen, T., Steffensen, I.E., Skadhauge, L.R., Kyvik, K.O., et al. (2010). Chronic mucus hypersecretion: prevalence and risk factors in younger individuals. Int. J. Tuberc. Lung Dis.  14, 1052-1058.
Hooper, L.G., Young, M.T., Keller, J.P., Szpiro, A.A., O'Brien, K.M., Sandler, D.P., et al. (2018). Ambient Air Pollution and Chronic Bronchitis in a Cohort of U.S. Women. Environ. Health Persp. 126, 027005-027005.   
Kim, V., Han, M.K., Vance, G.B., Make, B.J., Newell, J.D., Hokanson, J.E., et al. (2011). The chronic bronchitic phenotype of COPD: an analysis of the COPDGene Study. Chest 140, 626-633.  Kim, V., Oros, M., Durra, H., Kelsen, S., Aksoy, M., Cornwell, W.D., et al. (2015). Chronic Bronchitis and Current Smoking Are Associated with More Goblet Cells in Moderate to Severe COPD and Smokers without Airflow Obstruction. PLoS ONE 10(2), e0116108. 
Liu, Z., Geng, W., Jiang, C., Zhao, S., Liu, Y., Zhang, Y., et al. (2017). Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats. Exp. Biol. Med. 242, 1534-1541. 

Martinez, C.H., Kim, V., Chen, Y., Kazerooni, E.A., Murray, S., Criner, G.J., et al. (2014). The clinical impact of non-obstructive chronic bronchitis in current and former smokers. Respir. Med. 108, 491-499.

Regalado, J., Pérez-Padilla, R., Sansores, R., Páramo Ramirez, J.I., Brauer, M., Paré, P., et al. (2006). The effect of biomass burning on respiratory symptoms and lung function in rural Mexican women. Am. J. Resp. Crit. Care Med. 174, 901-905.

Shim, J.J., Dabbagh, K., Ueki, I.F., Dao-Pick, T., Burgel, P.R., Takeyama, K., Tam, D.C.W., and Nadel, J.A. (2001). IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils. Am. J. Physiol. Lung Cell. Mol. Physiol. 280, L134-140.

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

Song, L., Tang, H., Liu, D., Song, J., Wu, Y., Qu, S., and Li, Y. (2016). The chronic and short-term effects of gefinitib on airway remodeling and inflammation in a mouse model of asthma. Cell. Physiol. Biochem. 38, 194-206.

Stott-Miller, M., Müllerová, H., Miller, B., Tabberer, M., El Baou, C., Keeley, T., et al. (2020). Defining Chronic Mucus Hypersecretion Using the CAT in the SPIROMICS Cohort. Int. J. Chron. Obstruct. Pulmon. Dis. 15, 2467.

Sunyer, J., Jarvis, D., Gotschi, T., Garcia-Esteban, R., Jacquemin, B., Aguilera, I., et al. (2006). Chronic bronchitis and urban air pollution in an international study. Occup. Environ. Med. 63, 836-843. 

Vestbo, J. (2002). Epidemiological studies in mucus hypersecretion. Novartis Found. Symp. 248, 3-12; discussion: 12-19, 277-282.

Vlahos, R., and Bozinovski, S. (2015). Preclinical murine models of chronic obstructive pulmonary disease. Eur. J. Pharmacol. 759, 265-271.

Wang, H., Yang, T., Wang, T., Hao, N., Shen, Y., Wu, Y., et al. (2018). Phloretin attenuates mucus hypersecretion and airway inflammation induced by cigarette smoke. Intl. Immunopharmacol. 55, 112-119.

Yang, T., Luo, F., Shen, Y., An, J., Li, X., Liu, X., ... & Wang, T. (2012). Quercetin attenuates airway inflammation and mucus production induced by cigarette smoke in rats. Intl. Immunopharmacol. 13, 73-81.
Zemp, E., Elsasser, S., Schindler, C., Kunzli, N., Perruchoud, A.P., Domenighetti, G., et al. (1999). Long-term ambient air pollution and respiratory symptoms in adults (SAPALDIA study). Am. J. Resp. Crit. Care Med. 159, 1257-1266.