Proposed Terms

Below the reader will find, first, a draft list of proposed definitions by Richard Scheuermann, Werner Ceusters, and Barry Smith for the meeting titled: Signs, Symptoms and Findings: First Steps Toward an Ontology of Clinical Phenotypes (September 3-4, 2008). Then, the reader will find emails with comments pertaining to the proposed definitions from a few of those who participated in the meeting.

Diseases, Signs and Symptoms: Draft List of Proposed Definitions

We use ‘bodily feature’ to designate biological qualities, processes or structures of an organism such as blond hair, coughing, swelling.

We use ‘clinically normal’ to designate bodily features of a human being that are typically not associated with pain or other feelings of illness, with dysfunction, or with other indications of enhanced morbidity.

We use ‘homeostasis’ to designate the state in which the bodily processes of the organism are regulated in such a way as to (1) maintain bodily features within a certain homeostatic range and (2) respond successfully to departures from this range caused by external influences. During homeostasis the organism continually assesses its current state to determine if its bodily features fall within this range.

Homeostatic Range =def. The range of types of bodily features whose maintenance is continuously sought by an organism in the state of homeostasis.

Normal Homeostasis =def. Homeostasis of a type that is clinically normal for a human being of a given type and age in a given environment.

Abnormal Homeostasis =def. Homeostasis of a type that is not normal.

Disorder =def. A bodily structure in a human being that is clinically abnormal.

Etiological Process =def. A biological process in a human being that leads to a disorder.

Pathological Process =def. A biological process in a human being that is caused by a disorder.

Acute Pathological Process =def. A pathological process terminating with a resolution of the disorder and a return to normal homeostasis.

Acute Disorder =def. A disorder that leads to an acute pathological process.

Chronic Pathological Process =def. A pathological process that results from an adaptation on the part of the patient to a level of abnormal homeostasis.

Chronic Disorder =def. A disorder that, in the absence of intervention, would typically lead to a chronic pathological process.

Progressive Pathological Process =def. A pathological process that deviates increasingly from homeostasis in such a way that the re-establishment of homeostasis is precluded.

Progressive Disorder =def. A disorder that, in the absence of intervention, would lead to a progressive pathological process.

[1] Types of Pathological Process

Physical Examination =def. A sequence of acts of observing eliciting responses, and measuring the bodily features of a patient, occurring in the context of a clinical encounter.

Sign =def. A bodily feature of the patent that is observed in a physical examination and is hypothesized by the clinician to be a disorder or a manifestation of a disorder.

Symptom =def. A quality of the patient that is observed and can be observed only by the patient and is of the type that can be hypothesized by the patient as a manifestation of a disorder.

Laboratory Test =def. A laboratory assay that has as input a specimen derived from the patient, and as output a result that represents a quality of the patient.

Laboratory Finding =def. The representation of a quality of a patient that is the output of a laboratory test.

Clinical Finding =def. A representation of a bodily feature of a patient that is recorded by a clinician because the feature is hypothesized to be of clinical significance.

Clinical Phenotype =def. A constellation of those types of bodily features that are associated with a disorder at each stage of its development.

Clinical Picture =def. A representation of a clinical phenotype as instantiated in a given patient that is inferred from the constellation of laboratory and clinical findings available to the clinician about a given a patient at any given stage.

Diagnosis =def. The conclusion of an interpretive process that has as input a clinical picture of a given patient and as output an assertion to the effect that the patient has a disorder of such and such a type.

From: Xia, Ashley (NIH/NIAID) [E] [2] Sent: Tuesday, September 02, 2008 10:54 AM Subject: RE: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

Hi Richard

I would like to suggest to add a concept of Homeostatic Profile. The current concept of Homeostatic Range is good for a single measure of a sign, symptom or finding. Homeostatic Profile is good for a collection of homeostatic ranges of a homeostatic state.

Ashley

From: Kent Spackman [3] Sent: Tuesday, September 02, 2008 2:00 PM Subject: RE: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

I haven’t spent much time examining these proposed definitions, but thought I would give you my initial ‘off-the-cuff’ reaction in the form of questions (see attached). There may be good answers to some of these questions – in fact I hope there are. But I suspect I can generate a number of additional difficult questions on further reflection. The general ‘gist’ of the terms is easy to grasp, of course, but I think it would be unwise to underestimate the degree of difficulty of getting good definitions – and getting consensus about the meanings.

I would prefer to back up a step and try to answer two questions: 1) What are the fundamental types of things for which we need ontological categories? (Do we really need to differentiate “signs” from “symptoms”?) 2) What are the criteria by which we can judge whether we have good categories and good definitions? And I’d like to propose one important criterion. It is: the degree to which ordinary clinicians can understand and reproducibly apply the definitions.

Kent Spackman

From: Sivaram Arabandi [4] Sent: Tuesday, September 02, 2008 3:00 PM Subject: Re: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

I can see that the discussion is already getting off the ground and want to add a couple of thoughts. The workshop and the definitions of terms here (like 'Normal Homeostasis', 'Disorder' etc) are focused with the context 'human beings'. However the terms themselves are equally applicable in the more general sense to all animals. It may be useful to provide a broader definition because of the interplay between humans and animals (infectious diseases and their accompanying signs and symptoms - eg. rabies) as well as translational research.

Sivaram

From: Anita Burgun-Parenthoine [5] Sent: Tuesday, September 02, 2008 4:14 PM Subject: Re: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

Thanks for sharing these questions. I have two comments: - phenotypes (as well as observable entities) may be normal. It's interesting to mention that in MPO the synonyms for normal phenotype are 'viable' and 'fertile'.... - As Kent already said, some distinctions are difficult to get. For example, the distinction between chronic disorder and progressive disorder is difficult in practice as many chronic diseases end up with complications. Looking forward to the workshop, Anita

From: John Armstrong [6] Sent: Tuesday, September 02, 2008 5:34 PM Subject: RE: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

Richard,

From the content of the document you distributed involving disorders, findings, signs, symptoms, and processes, I gather that we will be facing some difficult conceptual issues related to classifying subsumption relations for which there do not appear to be intuitive child-parent links (e.g. those relating findings and disorders.) This is a constant challenge we face at Lead Horse Technologies, whether we are browsing SNOMED-CT or developing and editing our own, proprietary ontologies. There are approaches aimed at solving this dilemma, used by us and others, but they often can involve labor intensive curation and constant editing. If it’s not too late, I’d like to propose that topics discussed at the workshop this week include the idea that dilemmas like the one described here may be approached through tying the curation of intraontological relations not to intelligent design but to evolution – that is, linking the curation of subsumption relationships to actual clinical enquiries received from practicing clinicians rather than to the efforts of ontology development professionals such SNOMED-CT editors. This would boil down to applying a wiki-approach to ontology evolution and it is one that we are working on at Lead Horse. Food for discussion, even if only over a glass of wine.

Thanks, and I’m looking forward to the workshop. John

From: Colombo Gianluca [7] Sent: Tuesday, September 02, 2008 7:34 PM Subject: R: Signs Symptoms and Findings Workshop: Definitions Proposed for Discussion

Dear all, it is a pleasure to contribute to the discussion.

We would like to bring up two general points, and then proceed to a more detailed discussion of the proposed definitions.

First of all, a remarkable aspect of the diagnostic activity is that certain observations are performed, in order to reconstruct the state of a patient; the state itself is not fully/directly observable (e.g. diabetes cannot be observed per se); the observables collected during the diagnostic activity are interpreted by the clinician, according to some explicit theory and/or his experience, in order to fully reconstruct such state. We therefore deem important to disinguish between what is observed and what is inferred/reconstructed. Also the methodology/istrumentation for the observation, and the criteria for the inference/reconstruction play an importat role. Second, looks like that the notion of disorder plays a pivotal role. A disorder must ncessarily be an anomaly of structure. What is the rationale behind this choice?

Best, Gianluca Colombo and Daniele Merico

HERE ARE OUR COMMENTS:

Signs, Symptoms and Findings: Draft List of Definitions Proposed for Discussion

We use ‘bodily feature’ to designate biological qualities, processes or structures of an organism such as blond hair, coughing, swelling.

We use ‘clinically normal’ to designate bodily features of a human being that are typically not associated with pain or other feelings of illness, with dysfunction, or with other indications of enhanced morbidity. How is dysfunction defined?

We use ‘homeostasis’ to designate the state in which the bodily processes of the organism are regulated in such a way as to (1) maintain bodily features within a certain homeostatic range and (2) respond successfully to departures from this range caused by external influences. During homeostasis the organism continually assesses its current state to determine if its bodily features fall within this range.

Homeostatic Range =def. The range of types of bodily features whose maintenance is continuously sought by an organism in the state of homeostasis.

Normal Homeostasis =def. Homeostasis of a type that is clinically normal for a human being of a given type and age in a given environment.

Abnormal Homeostasis =def. Homeostasis of a type that is not normal.

Disorder =def. A bodily structure in a human being that is clinically abnormal. 1) Why a structure, and not a quality or process? What is the rationale? 2) A disorder can be both a cause and an effect? From the poin of view of etiology, it aperas to be neuter.

Etiological Process =def. A biological process in a human being that leads to a disorder. Why introducing the notion of etiological process but not of etiological factor?

Pathological Process =def. A biological process in a human being that is caused by a disorder. 1) Why is a pathological process interesting? Is it the connection between the disorder and the symptoms/signs, or the patient’s malaise, or morbidity? 2) A biological process ensuing a disorder may be physiological rather than pathological (e.g. wound healing), if pathological implicitly means “associated with pain or other feelings of illness, with dysfunction, or with other indications of enhanced morbidity” (quoted from clinically normal).