Asthma is caused by or worsened by different things in different people. It is because of
these differences that not all people with asthma respond the same to all treatments and
medicines. If the investigators can better identify the changes in the airways or breathing
pipes in patients with asthma, the investigators may be able to help patients make better
choices about the medicines or treatments that are most likely to work best for each patient.
This research study is about one specific factor that is known to affect asthma in some
patients. It involves an increase in the activity of an enzyme that is in people's airways.
An enzyme is something that helps a chemical reaction to occur. The enzyme the investigators
are studying in this research study is called GSNOR (S-nitrosoglutathione reductase) , and
when the activity of this enzyme is increased, the result is that there is less GSNO
(S-nitrosoglutathione) . GSNO is a chemical that protects people's airways. The initials
stand for S-nitrosoglutathione, (pronounced s-nahy-troh-soh-gloo-tuh-thahy-ohn), and it is
naturally produced by the body. It has an important role in regulating respiratory function
(breathing) and preventing inflammation (swelling) in the respiratory tract (throat, airways,
and lungs).
The amount of GSNO found in the body is controlled by the enzyme GSNOR (S-nitrosoglutathione
reductase). GSNOR breaks down GSNO. Too much GSNOR leads to low levels of GSNO, and that can
cause inflammation (swelling) and loss of airway function in some asthma patients.
The only way to measure GSNOR levels currently is with a bronchoscopy procedure where a scope
is inserted into the patient's airways, often under sedation. This research study is being
done to test the accuracy of another type of test that can be done in the doctor's office,
rather than in a procedure area. This non-invasive diagnostic test, called a GSNO Challenge
test, may be able to identify which asthma patients have increased activity of the airway
enzyme GSNOR. The investigators are also studying the phenotypes (observable traits) in
asthma patients with increased levels of GSNOR. If this research study is successful, in the
future (after this research study is done). The investigators may be able to offer a
cost-effective and non-invasive way to identify patients who have higher GSNOR activity
levels and offer personalized treatments.
The GSNO Challenge test includes giving an investigational drug to breathe in (inhale). The
investigational drug is GSNO. "Investigational" means the drug is not approved by any
regulatory agencies including the Food and Drug Administration (FDA), and is still being
tested for safety and effectiveness. The research is registered with the FDA, but again the
GSNO treatment in this study (administered during the GSNO challenge testing) is not an
approved treatment or diagnostic test for asthma.
Phase:
Early Phase 1
Details
Lead Sponsor:
James Reynolds
Collaborators:
Case Western Reserve University National Heart, Lung, and Blood Institute (NHLBI) University Hospitals Cleveland Medical Center