Key Event Title
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP|
|Decreased lung function||KeyEvent|
Key Event Description
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).
How It Is Measured or Detected
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 standradized measure exists.
Clinically, coughing and sputum production for >3 months in at least two consecutive years is defined as (chronic) mucus hypersecretion (Vestbo, 2002). As such, diagnosis depends on the extent of medical examination, including questioning the patient and subject recall. Current clinical practice, however, does not include a quantitative measure of mucus hypersecretion.
Domain of Applicability
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).
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.
Chen, P., Deng, Z., Wang, T., Chen, L., Li, J., Feng, Y., ... & Ou, X. (2013). The potential interaction of MARCKS-related peptide and diltiazem on acrolin-induced airway mucus hypersecretion in rats. Intl Immunopharmacol 17, 625-632.
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. AmJ Resp Cell Mol Biol 38, 446-454.
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.
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.
Vestbo, J. (2002). Epidemiological studies in mucus hypersecretion. Novartis Found Symp 248, 3-12; discussion: 12-19, 277-282.
Wang, H., Yang, T., Wang, T., Hao, N., Shen, Y., Wu, Y., ... & Wen, F. (2018). Phloretin attenuates mucus hypersecretion and airway inflammation induced by cigarette smoke. Intl Immunopharmacol 55, 112-119.