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1.  Multiple Flow Rates Measurement of Exhaled Nitric Oxide in Patients with Sarcoidosis: A Pilot Feasibility Study 
Fraction of end tidal exhaled nitric oxide (FeNO) has been introduced as a non-invasive marker of airway inflammation in patients with asthma and may have value in monitoring disease activity in patients with sarcoidosis. This pilot study explored: 1) feasibility of the multiple flow rates maneuver to estimate alveolar (CAlvNO) and airway wall (JAWNO) NO in patients with sarcoidosis; and 2) utility of exhaled NO (FeNO, CAlvNO and JAWNO) measurements to detect and monitor treatment response in patients with active pulmonary sarcoidosis. Patients with sarcoidosis (n=42) and healthy non-smokers (n=20) underwent FeNO measurement at 7 flow-rates (50 to 400 ml/s). Using the Tsoukias and George (1998) model, CAlvNO and JAWNO were estimated. Both patients and healthy non-smokers were able to perform the multiple flow rates maneuver without discomfort, with first measurement success rate of 57% and 65%, respectively. No significant difference was found between patients with sarcoidosis and healthy non-smokers in exhaled NO. None were correlated with pulmonary function tests, except a significant negative correlation between CAlvNO and FVC% (p=0.001) and DLCO% (p=0.012). In 8 patients with active sarcoidosis, FeNO, CAlvNO or JAWNO were not different from those of patients with inactive sarcoidosis. Treatment of active sarcoidosis using oral prednisone and methotrexate did not show any consistent pattern of changes in CAlvNO or JAWNO. Due to a large inter-subject variability and difficulty controlling use of the inhaled corticosteroids, exhaled NO measurement did not appear to be a clinically useful method of monitoring disease progression in sarcoidosis.
PMCID: PMC2889917  PMID: 20560290
pulmonary sarcoidosis; exhaled nitric oxide; multiple flow- rates maneuver
Chronic respiratory disease  2009;6(1):19-29.
Exhaled nitric oxide (eNO) utilized as an aid to the diagnosis and management of lung disease is receiving attention from pulmonary researchers and clinicians alike because it offers a noninvasive means to directly monitor airway inflammation. Research evidence suggests that eNO levels significantly increase in individuals with asthma prior to diagnosis, decrease with inhaled corticosteroid administration, and correlate with the number of eosinophils in induced sputum. These observations have been used to support an association between eNO levels and airway inflammation. This review presents an update on current opportunities regarding use of eNO in patient care, and more specifically, on its potential usage for asthma diagnosis and monitoring. The review will also discuss factors that may complicate use of eNO as a diagnostic tool, including changes in disease severity, symptom response, and technical measurement issues. Regardless of the rapid, convenient, and noninvasive nature of this test, additional well-designed, long-term longitudinal studies are necessary to fully evaluate the clinical utility of eNO in asthma management.
PMCID: PMC2724767  PMID: 19176709
Exhaled Gas Analysis; Nitric Oxide; Lung Inflammation; Asthma
3.  Non-invasive measurements of exhaled NO and CO associated with methacholine responses in mice 
Respiratory Research  2008;9(1):45.
Nitric oxide (NO) and carbon monoxide (CO) in exhaled breath are considered obtainable biomarkers of physiologic mechanisms. Therefore, obtaining their measures simply, non-invasively, and repeatedly, is of interest, and was the purpose of the current study.
Expired NO (ENO) and CO (ECO) were measured non-invasively using a gas micro-analyzer on several strains of mice (C57Bl6, IL-10-/-, A/J, MKK3-/-, JNK1-/-, NOS-2-/- and NOS-3-/-) with and without allergic airway inflammation (AI) induced by ovalbumin systemic sensitization and aerosol challenge, compared using independent-sample t-tests between groups, and repeated measures analysis of variance (ANOVA) within groups over time of inflammation induction. ENO and ECO were also measured in C57Bl6 and IL-10-/- mice, ages 8–58 weeks old, the relationship of which was determined by regression analysis. S-methionyl-L-thiocitrulline (SMTC), and tin protoporphyrin (SnPP) were used to inhibit neuronal/constitutive NOS-1 and heme-oxygenase, respectively, and alter NO and CO production, respectively, as assessed by paired t-tests. Methacholine-associated airway responses (AR) were measured by the enhanced pause method, with comparisons by repeated measures ANOVA and post-hoc testing.
ENO was significantly elevated in naïve IL-10-/- (9–14 ppb) and NOS-2-/- (16 ppb) mice as compared to others (average: 5–8 ppb), whereas ECO was significantly higher in naïve A/J, NOS-3-/- (3–4 ppm), and MKK3-/- (4–5 ppm) mice, as compared to others (average: 2.5 ppm). As compared to C57Bl6 mice, AR of IL-10-/-, JNK1-/-, NOS-2-/-, and NOS-3-/- mice were decreased, whereas they were greater for A/J and MKK3-/- mice. SMTC significantly decreased ENO by ~30%, but did not change AR in NOS-2-/- mice. SnPP reduced ECO in C57Bl6 and IL-10-/- mice, and increased AR in NOS-2-/- mice. ENO decreased as a function of age in IL-10-/- mice, remaining unchanged in C57Bl6 mice.
These results are consistent with the ideas that: 1) ENO is associated with mouse strain and knockout differences in NO production and AR, 2) alterations of ENO and ECO can be measured non-invasively with induction of allergic AI or inhibition of key gas-producing enzymes, and 3) alterations in AR may be dependent on the relative balance of NO and CO in the airway.
PMCID: PMC2474844  PMID: 18505586

Results 1-3 (3)