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How Is Asthma Related To Chronic Obstructive
Pulmonary Disease?
Though they are different diseases, asthma and COPD
affect the human body in a similar way. In asthma,
allergens irritate the lungs, in COPD, this is done
by cigarette smoke. This irritation inflames the sufferer's
airways, which the muscles then close, creating a narrowing
effect.
Research done at the University over the past 15 years
has found that the muscle layer in the airway is more
complex than has traditionally been thought. As well
as going into spasm during asthma and COPD attacks
the muscle layer produces a wide range of mediators
and cytokines — proteins that act as chemical
signallers when it comes into contact with allergens
or cigarette smoke. In asthma and COPD sufferers, these
proteins are produced by stimulation of airway muscle
cell walls in the lungs, releasing intracellular signalling
proteins called 'transcription factors' which alter
the DNA of the cell and activate messenger RNA. It
is these 'transcription factors' which activate the
inflammation by causing release of mediators and cytokines.
The activation status of these transcription factors
is determined by the balance between two competing
groups of enzymes called histone acetyl transferase
(HATs) and histone deacetylases (HDACs). In asthma
and COPD sufferers the balance is altered so that the
HATs are activated and HDACs suppressed with the result
that inflammation is switched on. The investigators
at the University think that if the balance could be
restored by inactivating HATs then the mediators and
cytokines will be switched off and inflammation dampened
down.
By exploring plant extracts that may reduce the activation
of HATs within airway cells, the researchers may isolate
compounds that could be used to suppress inflammation
in respiratory disease. Any drug successfully synthesised
from such compounds could potentially revolutionise
the treatment of respiratory disease. There is also
the potential to treat other inflammatory diseases,
such as rheumatoid arthritis and Inflammatory Bowel
Disease.
Professor Alan Knox, of the Division of Respiratory
Medicine at the University, said: “The majority
of people with asthma have access to reasonably good
anti-inflammatory treatments that can keep their conditions
under control. But up to 20 per cent of sufferers don't
respond well to the treatments currently available.
And when it comes to COPD, anti-inflammatory drugs
aren't very effective.
“By tracking the process which triggers the
inflammation and then identifying the compounds that
inhibit or activate these crucial enzymes, we could
put into motion the development of a drug which could
have a huge impact on the lives of those suffering
from respiratory and other inflammatory diseases.”
The Division of Respiratory Medicine at the University
has been awarded a total of £1.24m in grants
to study respiratory disease. The Wellcome Trust has
awarded Prof Alan Knox and Dr Linhua Pang £700,000
to research transcriptional control of inflammatory
gene expression in asthma — allowing the team
to examine the part inflammatory mediators play in
the way asthma sufferers react to allergens. A second
grant of £540,000 from MRC to Prof Knox and his
colleagues Prof Peter Fischer and Prof David Heery
will explore histone acetyl transferase (HAT) inhibitors
in asthma and COPD. This study will investigate a bank
of plant extracts at the University of Strathclyde,
seeking compounds that could combat the intercellular
processes that result in the symptoms of asthma and
COPD — inflammation of the airways which can
lead to coughing, breathlessness and increased chest
infections. |