Medieval thinking on the etiology of disease showed the influence of Galen and of Hippocrates.[6] Medieval European doctors generally held the view that disease was related to the air and adopted a miasmatic approach to disease etiology.[7]
In epidemiology, several lines of evidence together are required to for causal inference. Austin Bradford Hill demonstrated a causal relationship between tobacco smoking and lung cancer, and summarized the line of reasoning in the Bradford Hill criteria, a group of nine principles to establish epidemiological causation. This idea of causality was later used in a proposal for a Unified concept of causation.[8]
Disease causative agent
The infectious diseases are caused by infectious agents or pathogens. The infectious agents that cause disease fall into five groups: viruses, bacteria, fungi, protozoa, and helminths (worms).[citation needed]
The term can also refer to a toxin or toxic chemical that causes illness.
Chain of causation and correlation
Further thinking in epidemiology was required to distinguish causation from association or statistical correlation. Events may occur together simply due to chance, bias or confounding, instead of one event being caused by the other. It is also important to know which event is the cause. Careful sampling and measurement are more important than sophisticated statistical analysis to determine causation. Experimental evidence involving interventions (providing or removing the supposed cause) gives the most compelling evidence of etiology.[citation needed]
Related to this, sometimes several symptoms always appear together, or more often than what could be expected, though it is known that one cannot cause the other. These situations are called syndromes, and normally it is assumed that an underlying condition must exist that explains all the symptoms.[citation needed]
Other times there is not a single cause for a disease, but instead a chain of causation from an initial trigger to the development of the clinical disease. An etiological agent of disease may require an independent co-factor, and be subject to a promoter (increases expression) to cause disease. An example of all the above, which was recognized late, is that peptic ulcer disease may be induced by stress, requires the presence of acid secretion in the stomach, and has primary etiology in Helicobacter pylori infection. Many chronic diseases of unknown cause may be studied in this framework to explain multiple epidemiological associations or risk factors which may or may not be causally related, and to seek the actual etiology.
An endotype is a subtype of a condition, which is defined by a distinct functional or pathobiological mechanism. This is distinct from a phenotype, which is any observable characteristic or trait of a disease, such as morphology, development, biochemical or physiological properties, or behavior, without any implication of a mechanism. It is envisaged that patients with a specific endotype present themselves within phenotypic clusters of diseases.
One example is asthma, which is considered to be a syndrome, consisting of a series of endotypes.[9] This is related to the concept of disease entity.
Other example could be AIDS, where an HIV infection can produce several clinical stages. AIDS is defined as the clinical stage IV of the HIV infection.[10]
^"Aetiology". Oxford English Dictionary (2nd ed.). Oxford University Press. 2002. ISBN0-19-521942-2.
^Greene J (1996). "The three C's of etiology". Wide Smiles. Archived from the original on 2007-06-30. Retrieved 2007-08-20. Discusses several examples of the medical usage of the term etiology in the context of cleft lips and explains methods used to study causation.
^Lötvall, J.; Akdis, C. A.; Bacharier, L. B.; Bjermer, L.; Casale, T. B.; Custovic, A.; Lemanske, R. F. Jr.; Wardlaw, A. J.; Wenzel, S. E.; Greenberger, P. A. (2011). "Asthma endotypes: A new approach to classification of disease entities within the asthma syndrome". J Allergy Clin Immunol. 127 (2): 355–60. doi:10.1016/j.jaci.2010.11.037. PMID21281866.
