Elitech NANODUCT 1030 User Manual page 61

Appendix H: Supplemental Information
Cystic Fibrosis: A Brief Description of the Disease
Cystic fibrosis of the pancreas (or mucoviscidosis) is due to one of the many known 'inborn errors of
metabolism' that are fundamentally the result of aberrations in the structure of the genetic material. It is
classed as lethal because of the very poor prognosis afforded to sufferers. The inheritance is autosomal
recessive, so that an affected child must inherit one defective gene from each of the parents to be
homozygotic. Such parents must then at the least be carriers (heterozygotes). The distribution of the
genetic anomaly varies with racial types. It is predominantly associated with Caucasians in whom it occurs
in about 1 in every 1500 to 2000 live births.
The symptoms of the disease are manifold; however, they are not strictly specific and hence physicians
often have difficulty in distinguishing CF from other childhood diseases on the basis of medical diagnosis
alone. The most serious clinical features are the pulmonary problems stemming from abnormally viscous
exudates in the lungs, requiring urgent physiotherapy and antibiotic treatment to offset the ever-present risk
of pneumonia. The pancreas is also affected by over-viscous secretions that reduce its output of digestive
enzymes; thus, the child tends to fail to thrive because the food ingested passes through the alimentary
canal without the normal enzymic breakdown necessary for absorption of nutrients. Fortunately, the latter
problem is relatively easily corrected by the addition of animal pancreatic extracts to the diet. The use of
"pancreas" in the disease name arose because of the identification (in 1938) of pancreatic abnormalities
during post-mortem examination of children that had died with a set of symptoms that were not as yet
associated with a specific illness. It should be noted here that CF sufferers may differ quite widely in the
degree to which they exhibit the various symptoms. Some may be relatively less affected in the respiratory
airways; others may show more serious pancreatic problems. A feature of the inheritance is that carriers do
not exhibit the symptoms of CF.
In 1953, it was found that children afflicted by the disease are prone to acute hyponatremia during hot
weather. Investigations on the cause of the loss of sodium showed that the eccrine sweat of children with
CF contains 3 to 4 times as much salt as that of unaffected subjects. Subsequent work showed that this
salt increase is not observed in presumed carriers. This was the first intimation that a laboratory test for
the disease was conceivable. The sweat test was born and remains to this day the principal laboratory
diagnostic test for this disease. In recent years the discovery of "the CF gene" promised a new laboratory
diagnostic approach. Intensive studies of this gene have revealed hundreds of variants that may, or may
not, produce the typical CF symptoms.
There is no doubt that in the future, this research will illuminate the effects of different genetic abnormalities
on the biochemical patterns of the individual. However, the sweat test will remain the definitive laboratory
diagnostic test for some time yet.
The Evolution of Sweat Test Methods
The sweat test has traditionally involved three separate, sequential procedures — stimulation of the sweat
glands, collection of their secretion, and sweat analysis. Early stimulation procedures involved total body
heating followed by placing the patient in a bag, or, later by heating followed by collection from a limited
area of skin covered by a hermetically sealed absorptive pad. Both of these methods endangered the
infants and proved unsatisfactory.
The heating was eventually avoided by using pilocarpine iontophoresis to induce the glands to sweat
maximally. Following this, the sweat was collected in a pre-weighed pad and re-weighed, eluted and
analyzed.
The method is usually known as the Gibson and Cooke
(quantitative pilocarpine iontophoresis test). This procedure has persisted over the years and is still being
performed, particularly by CF centers. It is time-consuming and tedious, requiring many manipulations
where human error may intervene, and in one particular step offers technical difficulties that virtually ensure
some degree of error, particularly when the sweat sample size is very small.
Laboratorians in CF centers who specialize in this method develop the requisite skill to maintain reasonably
accurate results, but this is generally not the case in outlying clinics and hospitals, where the test is only
occasionally requested, leading to unacceptably high risk of false results.
pad absorption sweat test or the QPIT
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