Title: Exhaled Nitric Oxide Measured using TDLAS Insensitivity to High Atmospheric Nitric Oxide Concentrations
1Exhaled Nitric Oxide Measured using
TDLASInsensitivity to High Atmospheric Nitric
Oxide Concentrations
Mark Camp, M.D., F.A.C.P., F.C.C.P. The Lung
Center, Norman, OK James D. Jeffers, Chad Roller,
Khosrow Namjou, Ph.D. Ekips Technologies, Inc.,
Norman, OK Patrick J. McCann, Ph.D. University of
Oklahoma, School of Electrical and Computer
Engineering
ACAAI Annual Meeting San Antonio, Texas November
18, 2002
2Study Objectives
- Evaluate Tunable Diode Laser Absorption
Spectroscopy (TDLAS) as a new tool for exhaled
nitric oxide (eNO) measurements. - Use eNO to assess airway inflammation and monitor
therapy. - Determine if high levels of ambient NO affect eNO
measurements.
3Motivation
- Asthma is a chronic inflammatory disorder of the
lower airways - Working definition (NHLBI, 1995)
- High eNO levels are linked to inflammation.
- Spirometry provides only limited and indirect
information regarding airway inflammation.
4Nitric Oxide Biochemistry
Healthy Subjects cNOS L-arginine ? L-citrulline
NO
Effects of NO Vasodilatation Host Defense Smooth
Muscle Relaxation
Asthmatics cNOS L-arginine ? L-citrulline NO
iNOS L-arginine ? L-citrulline NO
Excessive NO is associated with airway
inflammation.
Constitutive and inducible nitric oxide
synthases (cNOS and iNOS) are genetically-produce
d enzymes
- iNOS Inhibitors
- Inhaled corticosteroids
iNOS Expression Caused by epithelial cell
exposure to specific cytokines and endotoxins
Epithelial Cell
? Inflammation ? High exhaled NO
5 NO Measurement Techniques
- Chemiluminescence
- Reaction with ozone
- Patients must exhale at constant flow rates
- Requires NO-free air to zero the instrument
- Requires calibration using standard reference
gases - Unreliable calibration gases can result in
unreliable data. - NO degrades to NO2
- TDLAS
- Molecules absorb IR light
- Simultaneous NO and CO2 detection improves
reliability - Patients can exhale at different flow rates
- No consumables
NO O3 ? NO2 h? (light)
Spectral Signals
6 eNO Measurements with TDLAS
Results in 20 seconds
7 Asthmatic Examples
Age 14, Male, Mild-Persistent Non-Treated
Age 5, Female, Mild-Persistent Corticosteriod
Treated
Normal Airway
Inflamed Airway
8Treatment Monitoring
9Air Pollution Effects?
- Nitric Oxide is a major component of smog.
- Automobile exhaust is primary source.
- Ambient NO (aNO) concentrations will vary with
geography, weather conditions (inversion layers),
and time of day.
10eNO not Affected by aNO
Low aNO (2 ppb)
High aNO (24 ppb)
Untreated Asthmatic
Untreated Asthmatic
Non- Asthmatic
Non- Asthmatic
Ambient Air Displaced by Breath
11Replication Precision
- TDLAS provides good replication precision in
spite of varying atmospheric NO levels.
Non-asthmatic volunteer over a three-month period
12Biochemistry of NO Absorption
- Ambient NO is rapidly absorbed by the airways and
not subsequently exhaled.
Airway Tissue
NO ROS ? NO2 and NO3
Endogenously-produced NO scavenges cytotoxic
reactive oxidative species (ROS). Dweik et
al., Proc. Natl. Acad. Sci. 98, 2622 (2001)
High eNO is possibly associated with a
protective mechanism in asthmatic airways.
13Conclusions and Future Work
- TDLAS successfully measured high eNO in untreated
asthmatics and low eNO in treated asthmatics and
non-asthmatics. - A reduction in eNO from more than 40 ppb to less
than 20 ppb over a 7-day period was observed
following anti-inflammatory treatment. - High levels of ambient NO are rapidly absorbed
and not subsequently exhaled. - Clinical trials are continuing.