Respiratory Function Conditioned By Inflammation Markers And Genetic Profile

There are close links between blood inflammatory markers,
such as C-reactive protein (CRP), and respiratory function.
So reveals a study to be published in the forthcoming issue
of the European Respiratory Journal (ERJ), the peer-reviewed
publication of the European Respiratory Society (ERS).


This original research by an international team provides additional
support for the idea that chronic obstructive pulmonary
disease (COPD) is not limited to the lungs, and is a more systemic
condition.


The results of the ERJ study also suggest that signs of systemic
inflammation may precede a deterioration in respiratory parameters,
which could have implications for the treatment of this type of
pathology.



While local inflammatory phenomena have been widely described in
connection with airway conditions, data on links between systemic
inflammation processes and respiratory parameters are rare.


To clarify such possible interactions, an international team headed
by Jordi Sunyer (Municipal Institute of Medical Research, IMIM,
Barcelona, Spain) undertook this groundbreaking study, which also
takes into account genetic polymorphisms coding for the principal
inflammatory markers. The team worked with colleagues based in Italy,
Germany and Finland.


CRP's key role


For this original study, the researchers selected 134 myocardial
infarction survivors, who were participants in the multicentre
AIRGENE study. The 134 volunteers, recruited an average of 2.7 years
after their last heart attack, were examined six times at four-week
intervals.


Each time they examined the subjects, the researchers carried out a
full set of tests for inflammation, measuring CRP, interleukin-6 and
fibrinogen. They also conducted genotyping of the 36 polymorphisms of
coding genes for these three inflammatory markers. In parallel,
respiratory function was explored using spirometric testing.


As a result, the authors of the ERJ article were able to clearly
observe an inverse correlation between blood levels of CRP and
interleukin-6 on the one hand, and respiratory volume on the other.
When other parameters were taken into account, this correlation was
found to be independent of smoking and factors connected with the
severity of the cardiac condition.


On studying the subjects' genetic profiles, Sunyer also observed that
certain (rare) variants of the CRP gene (polymorphism rs1205 and
haplotype 2) were associated with better respiratory parameters at
spirometric testing.


The study's authors note that these two variants had been linked to a
low CRP level in previous studies. "This suggests that heritability
of lung function, like basal CRP level, is partially controlled by
the CRP gene," they explain.


COPD: a systemic condition?


No link was found, however, between the interleukin-6 gene and
spirometric data. Respiratory function was also found to be
independent of serum levels of fibrinogen and its coding gene
polymorphism.


This research thus provides support for the increasingly popular idea
that COPD, which includes chronic bronchitis and emphysema, amongst
others, is a systemic condition and not only a respiratory disease.
If confirmed, this theory could have major practical consequences for
the treatment of COPD.


The results published in the forthcoming issue of theERJ also
suggest that signs of systemic inflammation could precede a
deterioration of respiratory parameters, which could be a useful
warning signal.


Sunyer remains cautious, however, pointing to the limitations of his
work: the small subject group makes it more difficult to provide
incontrovertible evidence of the role of a genotype variant.


Furthermore, the nature of the population studied (myocardial
infarction survivors) may explain the lack of associations between
respiratory function and fibrinogen, since most of the patients were
taking statins, which are known to reduce fibrinogen levels.


This is a preliminary study, Sunyer emphasises, and needs to be
confirmed by other research before its conclusions can be generalised.


Title Of The Original Article

Systemic inflammation, genetic susceptibility and lung function


The European Respiratory Journal is the peer-reviewed scientific publication
of the European Respiratory Society (more than 8,000 specialists in lung
diseases and respiratory medicine in Europe, the United States and
Australia).


European Respiratory Journal