The EASI model: A first integrative computational approximation to the natural history of COPD

PLoS One. 2017 Oct 10;12(10):e0185502. doi: 10.1371/journal.pone.0185502. eCollection 2017.

Abstract

The natural history of chronic obstructive pulmonary disease (COPD) is still not well understood. Traditionally believed to be a self-inflicted disease by smoking, now we know that not all smokers develop COPD, that other inhaled pollutants different from cigarette smoke can also cause it, and that abnormal lung development can also lead to COPD in adulthood. Likewise, the inflammatory response that characterizes COPD varies significantly between patients, and not all of them perceive symptoms (mostly breathlessness) similarly. To investigate the variability and determinants of different "individual natural histories" of COPD, we developed a theoretical, multi-stage, computational model of COPD (EASI) that integrates dynamically and represents graphically the relationships between exposure (E) to inhaled particles and gases (smoking), the biological activity (inflammatory response) of the disease (A), the severity (S) of airflow limitation (FEV1) and the impact (I) of the disease (breathlessness) in different clinical scenarios. EASI shows that the relationships between E, A, S and I vary markedly within individuals (through life) and between individuals (at the same age). It also helps to delineate some potentially relevant, but often overlooked concepts, such as disease progression, susceptibility to COPD and issues related to symptom perception. In conclusion, EASI is an initial conceptual model to interpret the longitudinal and cross-sectional relationships between E, A, S and I in different clinical scenarios. Currently, it does not have any direct clinical application, thus it requires experimental validation and further mathematical development. However, it has the potential to open novel research and teaching alternatives.

MeSH terms

  • Computer Simulation
  • Disease Progression
  • Disease Susceptibility
  • Dyspnea / physiopathology
  • Female
  • Humans
  • Inhalation Exposure / analysis*
  • Lung / physiopathology*
  • Male
  • Models, Statistical*
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / etiology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Ventilation / physiology
  • Severity of Illness Index
  • Smoking / physiopathology*
  • Smoking Cessation / statistics & numerical data
  • Time Factors

Grants and funding

This work was supported, in part, by Instituto de Salud Carlos III FEDER (PI15/00799 to AA, CP16/00039 and the COPD research program of CIBERES), SEPAR (PI065/2013) and IDIBAPS Cellex.