Key Event Title
|Level of Biological Organization|
Key Event Components
|respiratory function trait||decreased|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP|
|Decreased lung function||AdverseOutcome|
Key Event Description
Lung function is a clinical term referring to the physiological functioning of the lung, most often in association with the tests used to assess it. Inspired and expired lung volumes measured by spirometry are useful for detecting, characterizing and quantifying the severity of lung disease (Wanger et al., 2005). Decreased lung function presenting as reduced volume of air which is exhaled in the first second of the forced exhalation (FEV1), is a feature of obstructive pulmonary diseases (e.g. asthma, COPD) and can have a multitude of causes including exposure to cigarette smoke, dust, metals, organic solvents, asbestos, pathogens or genetic factors.
How It Is Measured or Detected
Unless accompanied by clinical symptoms such as shortness of breath or patient complaint, decreased lung function might go unnoticed. However, when indicated, physicians will refer to spirometry and/or plethysmography to assess both airflow and lung volume, important indicators of lung function. Extensive and widely accepted clinical guidelines exist for the performance and interpretation of spirometry and lung volume measurements (Miller et al., 2005a; Miller et al., 2005b; Pellegrino et al., 2005; http://goldcopdorg/).
Domain of Applicability
Lung function tests require compliance from the subject to execute breathing maneuvers required to measure air flow and lung function. This is not possible in laboratory animals, hence such measurements in mice and rats are generally based on forced maneuvers yielding lung function parameters that are difficult to compare to those in humans.
Regulatory Significance of the Adverse Outcome
While currently not considered a classical toxicological AO, decreased lung function has important clinical implications.
In COPD patients, the annual decline in FEV1 can give an indication of disease progression and treatment success (Vestbo et al., 2008). COPD patients exhibiting a rapid decline in FEV1 are at higher risk of exacerbations, increased hospitalization and early death (Wise et al., 2006; Celli, 2010). Reduced FEV1 also poses a risk for serious cardiovascular events and mortality associated with cardiovascular disease (Sin et al., 2005; Lee et al., 2015).
Celli, B. R. (2010). Predictors of mortality in COPD. Resp Med 104, 773-779.
Miller, M.R., Crapo, R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Enright, P., van der Grinten, C.M., and Gustafsson, P. (2005a). General considerations for lung function testing. Eur Resp J 26, 153-161.
Miller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Crapo, R., Enright, P., van der Grinten, C., and Gustafsson, P. (2005b). Standardisation of spirometry. Eur Resp J 26, 319-338.
Pellegrino, R., Viegi, G., Brusasco, V., Crapo, R., Burgos, F., Casaburi, R., Coates, A., van der Grinten, C., Gustafsson, P., and Hankinson, J. (2005). Interpretative strategies for lung function tests. Eur Resp J 26, 948-968.
Sin, D. D., Wu, L., & Man, S. P. (2005). The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature. Chest 127, 1952-1959.
Vestbo, J., Anderson, W., Coxson, H.O., Crim, C., Dawber, F., Edwards, L., Hagan, G., Knobil, K., Lomas, D.A., MacNee, W. and Silverman, E.K., 2008. Evaluation of COPD longitudinally to identify predictive surrogate end-points (ECLIPSE) (2008). Eur Respir J 31, 869-73.