Saturday, April 26, 2008

Etiology and Exercise (and Judith's Comments)

Reference:

Etiology of Chronic Fatigue Syndrome: Testing
Popular Hypotheses Using a National Birth Cohort
Study - see abstract, posted by Fred Springfield at
Co-Cure:
http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind0804a&L=co-cure&T=0&P=1270

http://www.cfids.org/cfidslink/2008/040903.asp?tr=y&auid=3544493

Etiology, Exercise and CFS
~~~~~~~~~~~~~~~~
By Suzanne Vernon, Phd

Hot off the press from the journal Psychosomatic
Medicine is a paper by Samuel B. Harvey, Michael
Wadsworth, Simon Wessely and Matthew Hotopf
entitled "Etiology of Chronic Fatigue Syndrome:
Testing Popular Hypotheses Using a National Birth
Cohort Study."

Despite the psychological spin they put on the
results, the findings in this paper validate what
many in the patient community describe regarding
activity levels prior to the onset of illness: "I was a
runner. . . "; "I loved to hike. . . "; "until I got CFS."

This is an important publication because of that
validation. This paper also reminds us of the
importance and possible impact of events that
happen across the lifespan.

Let's first break down the title so that we understand
what the study attempts to do.

Etiology is the study of causation. Even though many
investigators have searched for the cause of CFS, it
has proven to be elusive. There have been many
explanations as to why scientists haven't pinned
down a cause, but the most likely one is that CFS is
a complex, chronic disease resulting from a
combination of gene-environment interactions.

Chronic diseases like CFS are tough to study let
alone to identify a cause because--as the name
chronic implies and the definition insists upon--the
disease occurs over time. The term birth cohort
refers to a group of people enrolled in a study from
birth and followed for a certain period to evaluate
any number of issues across the lifespan.

Three of this study's investigators are from the
Institute of Psychiatry at King's College London and
the other, Professor Michael Wadsworth, is the
retired director of the Department of Epidemiology
and Public Health at University College London. This
is the department that operated the National Survey
of Health and Development, a British national birth
cohort survey established in 1946, originally to
investigate how lifespan health matters might affect
fertility and obstetric issues.

In this study, the investigators aimed to test a set
of hypotheses about the cause of CFS. They
examined whether there were increased rates of
allergy and asthma (referred to as atopic illness),
decreased levels of physical exercise and/or
increased childhood illnesses in people with CFS.

Since this is a birth cohort, each hypothesis tapped
into information from various ages. For example,
childhood illness was evaluated between the ages of
6 to 15 years. A history of atopic illness was taken
when the study subjects were 36 and 43 years old.
Information on physical activity was gathered across
the lifespan up to 53 years of age.

While there is a great deal of data on this cohort,
only information relevant to the above hypotheses
was analyzed. (You can read more about this cohort
and the kinds of information collected at
http://ije.oxfordjournals.org/cgi/reprint/35/1/49.pdf .)

The first step was to determine how many people in
this cohort self-reported a diagnosis of CFS. Of 2,983
participants, 10 men and 24 women (1%) reported a
diagnosis of CFS with fatigue symptoms starting
between 41 and 53 years of age.

When investigators looked at rates of childhood
illnesses that resulted in school absence or
hospitalization in these 34 people with CFS, they
were no different from the rest. There were also no
differences in the rates of atopic illness. And rather
than finding decreased levels of physical exercise,
the authors were surprised to find that the 34 people
with CFS had higher than average levels of exercise
throughout childhood and a lower body mass index
prior to their CFS diagnosis.

Interestingly, these same folks reported continued
exercise even after they began to experience early
symptoms of fatigue.


So does this study identify the cause of CFS as being
exercise? No. However, it did a reasonable job of
decreasing the possible importance of atopic illness,
lifetime inactivity or exercise phobia as causes of
CFS.

The authors also did a good job of acknowledging
some of the strengths and weaknesses of the study.
But the greatest weakness of this study (which was
not acknowledged) is using a national birth cohort
that was designed to study something else.

Since this particular British national birth cohort was
designed to study fertility and obstetric issues, the
information collected is particularly relevant to these
two health questions.

So some potentially CFS-relevant information may be
missing. For example, the information on childhood
illness is limited, and there's no information on
illnesses--in particular infectious disease
episodes--after age 15.

The information that was not collected from this
national birth cohort isn't the fault of the authors.

But rather than interpreting that the drive to be
physically active is a personality trait that
predisposes people to CFS, what might these
researchers have found if they had the information
and inclination to approach their investigation from a
gene-environment perspective?

There is sufficient evidence in the literature that
points to genetic vulnerability for CFS. There's also
extensive evidence documenting environmental
events, such as infectious mononucleosis, that can
trigger CFS.

Now we see a possible connection to body mass and
lifetime activity. So what happens to active
individuals who get the "flu" and return to that same
lifestyle after they feel they've recovered? It's time
for investigators to step out of their comfort zone
and step up to the task of connecting these
tantalizing bits of disparate information to get to the
cause(s) of CFS.


(c) 2006, The CFIDS Association of America, Inc.

Judith opines:

I recently posted to CO-CURE a post that had as its purpose my concern  that
the basic canons of scientific methodology, logic, sound medical thinking  had
been badly violated in an article that had been announced on CO-CURE.   That
article appeared in a recent issue of PSYCHOSOMATIC MEDICINE.  It's  title
stated that it was a study of the most popular etiological factors (I am  not
sure what "popular" meant but certainly suggested "broadly accepted" or at  least
"broadly written about by worthy clinical and lab researchers.

What I objected to was not that there wasn't a shred of truth in the  article
or that there was nothing worthwhile. 

Now, Suzanne Vernon, who I know or knew knows what scientific methodology 
is, writes to defend the article because it used one of the most substantial 
cohorts.

And it mentioned some factors that most of us know are oft predisposing 
factors in the illness, like a history of atopy. But one of the central  (among so
many) bafflements about ME fall within the term "exercise  intolerance." 
Since a long flare after an increase in (I prefer to use)  muscle exertion/muscle
stress, even when it is "happy" and very longed for,  which in some studies
has been shown to correlate with changes in certain  metabolites, even when
that muscle exertion while it's happening is experienced  as pleasure and thus
maybe "causes" good neurochemicals to rise (popularly  referred to as
"endorphins") one hypothesis that cannot be dismissed is that  despite emotional and
physiological plusses being produced by muscle activity at  varying levels for
different people or the same people at different times in  their illness such an
experience would/could lead to increasing the inclination  to "exert their
muscles."

Unless they are masochists, I suppose.  But I don't think that  personality
problem has been sufficiently studied in even a small cohort.

To continue: Despite the size of the cohort and despite the correct mention 
of atopy as (I don't know what loading atopy has as a predisposing factor or
if  it's been studied both as a physiological characteristic and as a
psycho-social  one, including its role in early family development experiences that
shaped our  ME patient, which in some cases might have invited overprotective
parenting  and possibly the tendency to fear healthy activity though in
adolescence that  can be rejected and would have to be subjected to a long term, even
if  retrospective study) that article did nothing absolutely nothing to provide
a  sound differential diagnosis (exhaustive list of possible causal
hypotheses) for  "exercise intolerance."

Atopy does not.  Atopy does not ipso facto lead a person to fear  activity even though it can, rationally, lead to avoidance behavior.  But  that study did
not study how childhood atopy that might very well have "caused"  certain
avoidance behaviors that those who seem to have ME have  perpetuated in their
personality a tendency towards over-generalized  avoidance.

That is an hypthosis that is worthy of study though well designed and as I 
said above long-term not just large cohort.  And there would need to be a 
control group of those who were atopic and didn't develop ME so that the 
difference between the groups could then be studied if atopy were to be a  helpful
thing to know about the complex etiology of ME, if indeed ME is one  thing, which
it probably is not, and is a cluster of illnesses.

I do not comprehend, truly, how anyone with any medico-scientific 
credentials, knowledgeable about ME could possibly validate that study (Wesseley  among others was an author; there were several others) as throwing light on 
anything we don't already know about atopy and ME, even though it could be a  worthy
thing to study. 

The content and the logic, the substance of a small cohort study can often 
be far more useful to further getting to some of the central connunundrums  of
ME.  Not the size of the cohort.

I am starting to wonder if the model of thinking found affecting too much  US
governmental policy isn't a model for some of what we are seeing in the 
so-called ME scientific thinking.

But, then, I'm just sick and am rather sensitive to such sloppy reasoning 
about ME.  And I am one who feels that psychological factors and behavioral 
tendencies play their role in etiology, though I do not think there is ANY 
evidence that those factors are the ones that will lead us to major palliation  or
cure.

Judith Wisdom




No comments: