Individual sensititivy for the development of interstitial lung diseases (ILD)

Interstitial lung diseases (ILD) is a collective noun for various chronic lung
diseases, including sarcoidosis and idiopathic lung fibrosis (IPF). Sarcoidosis
is a multi-systemic disease that includes damage to the lungs in 90% of the
patients. It*s difficult to give a concise definition of sarcoidosis, due to
the fact that its exact cause is still unknown, but generally the diseases can
be described as a systemic, granulomatous and antigen-driven disorder. IPF is a
disease of the lungs only, in which an unknown cause induces a strong
inflammation reaction leading to acute lung damage that ultimately results in
the formation of scar tissue and stiffness of the lungs.

Unfortunately, the exact cause of ILD is still unknown. It is suggested
that environmental and work-related exposure to various triggers can exert an
effect on the course of the diseases. Examples of such triggers include
viruses, bacteria, organic agents such as pollen and cotton dust and inorganic
agents like metals and talc. Since the exact cause of ILD is still unknown, it
is difficult to treat these diseases. Consequently, the current guideline is no
medication or anti-inflammatory agents in severe cases. Unfortunately, this
therapy is not completely effective.

Triggers that are suggested to cause ILD can exert their effects via
various mechanisms. On the one hand, they can induce an inflammatory reaction
as we recently demonstrated for various triggers including instillation
material and sicila (Boots et al, unpublished data). During such an
inflammatory reaction, cytokines are released that can induce oxidative stress,
i.e. an imbalance between the formation of and the protection against reactive
oxygen species (ROS), in various cells and tissues. On the other hand,
ILD-inducing triggers may directly cause an increased ROS production that
subsequently can evoke an inflammatory reaction. In other words, triggers that
are suggested to cause ILD may exert their effect by inducing an increased ROS
production as well as an enhanced inflammatory reaction.

The objective of the current study is to investigate the individual
sensitivity for the development of ILD after exposure to various triggers. Main
focus will be the differences in the formation of and the protection against
ROS as well as the occurring inflammatory reaction after exposure to such
triggers.
Furthermore, a simple blood test will be developed to study and
eventually even predict the individual reaction of subjects to various triggers.
Finally, to fully characterize the development of ILD after exposure to various
triggers, the exhaled air of patients will be studied in order to identify
specific markers of oxidative stress and damage.

This study is designed to investigate the individual sensitivity for the
development of ILD after exposure to various triggers. Furthermore, this study
will be used to develop a simple blood test in order to investigate or even
predict the individual reaction of subjects to various exposures. To this
extent, ILD patients will be asked to fill in 2 questionnaires regarding either
their possible exposures or their health and quality of life. Moreover, the
patients will be asked to donate 5L exhaled air and 20 ml blood.
Based on the questionnaires, the ten most frequently occurring triggers will be
selected. The individual sensitivity for the development of ILD will be tested
by ex vivo adding these triggers to the blood of each participant, after which
various markers of oxidative stress and inflammation will be measured. To study
the effects of triggers on individual level, all participants will also be
tested for their one specific exposure.
This study will be performed with 100 ILD patients in total, 50 sarcoidosis and
50 IPF patients. Patients will be recruited by their own physician, after which
the researcher will provide oral and written information in case patients are
interested.

The burden for the participants is minimal since they are only asked to donate
20 ml blood and 5 L exhaled air. Furthermore, they have to fill in 2
questionnaires, one regarding their possible exposures and one regarding their
health and quality of life.