Blood eosinophil numbers: the mirror of the eosinophil
compartment in health and disease.
Leo Koenderman and Marwan Hassani
- The role of eosinophils in allergic inflammation is well recognized,
but these cells have evolved for millions of years before the
evolution of T2 inflammation.
- In homeostasis these cells are found in multiple healthy tissues
including the lung parenchyma, but the function of
these resident eosinophils is unknown.
- As eosinophils are produced by the bone marrow (2,3) and are
distributed through the blood, the number of blood eosinophils is
associated with the numbers of cells found in the tissues in health
and disease. Indeed, the extend of T2-inflammation is mirrored by
higher numbers of eosinophils in het peripheral blood (2).
Stratification on blood eosinophil numbers identifies patients likely
to respond to IL-5(R) targeted therapy (see for a review (3)).(figure 1)
- Sputum eosinophilia is not specific for airway disease. It is also
increased in other eosinophil associated pathologies such as Crohn’s
disease4. Besides, the number of sputum eosinophils
is mainly not reproducible (5).
- Blood eosinophil numbers can easily and quantitatively be determined
in any hospital laboratory. This is in marked contrast to sputum
eosinophils where adequate determination of absolute eosinophil
numbers is impossible, because of the requirement of complex
processing of sputum samples (in a specialized laboratory) and the
lack of an adequate determination of sputum volume.
- No experimental data support the often made suggestion that sputum
cells represent tissue eosinophils. In fact, the scarce data available
show that tissue eosinophils exhibit a different phenotype than sputum
cells (6). Surely a cut-off value of the eosinophil percentage in
sputum obtained from the central airways, cannot easily be
translated to values found in the lower airways, that are more
relevant for asthma. Therefore, blood eosinophils as a reflection of
the total eosinophil compartment en route to tissues provides much
better, reproducible and quantifiable information.
- Eosinophils ending up in the sputum exhibit an activated phenotype
because of the process of adhesion and
trans-endothelial/stromal/epithelial migration rather than induced by
the disease process per se. Subtle (pre)-activation of eosinophils by
disease-associated signals can therefore only be measured in the
peripheral blood.
- It is clear that total eosinophil numbers in blood and tissue are
determined by two independent differentiation pathways (see figure):
IL-5 dependent (2) inflammatory eosinophils and IL-5-independent
resident cells (7). The total number of eosinophils in blood and
tissues will be the summation of the numbers of both phenotypes. It is
essential to develop markers for both phenotypes as the number of the
individual phenotypes will hold important information about the total
eosinophil compartment. More research around this critical issue is
warranted.
- Therefore, the specific determination of the absolute number ofinflammatory eosinophils in blood will be a great step forward.
Until then, several large field studies have already shown that total
blood eosinophil count, which can be quantified accurately and simply,
is a critical marker for the success of treatment of asthmatics with
eosinophil targeted drugs (3).
- In conclusion, sputum induction and analysis are inadequatefor the accurate determination of asthma phenotype and/or severity.
The determination of the numbers of resident and inflammatory
eosinophils in the peripheral blood is an ideal immunological
instrument to identify asthma patients eligible for treatment with
biologicals particularly when the resident and inflammatory
eosinophils can be quantified individually.