Extended Exhaled NO Measurement Differentiates between Alveolar and Bronchial Inflammation

Abstract

Lower respiratory tract inflammation can be detected by measuring exhaled nitric oxide (NO) concentration at a single exhalation flow rate, but this does not differentiate between alveolar and bronchial NO production. We assessed alveolar NO concentration and bronchial NO flux with an extended method of measuring exhaled NO at several exhalation flow rates in 40 patients with asthma, 17 patients with alveolitis, and 57 healthy control subjects. Bronchial NO flux was higher in asthma (2.5 +/- 0.3 nl/s, p < 0.001) than in alveolitis (0.7 +/- 0.1 nl/s) and healthy control subjects (0.7 +/- 0.1 nl/s). Alveolar NO concentration was higher in alveolitis (4.1 +/- 0.3 ppb, p < 0.001) than in asthma (1.1 +/- 0.2 ppb) and healthy control subjects (1.1 +/- 0.1 ppb). In asthma, bronchial NO flux correlated with serum level of eosinophil protein X (EPX) (r = 0.60, p < 0.001) and bronchial hyperresponsiveness (r = 0.55, p < 0.001). In alveolitis, alveolar NO concentration correlated inversely with pulmonary diffusing capacity (r = -0.55, p = 0.022) and pulmonary restriction. Glucocorticoid treatment or allergen avoidance normalized bronchial NO flux in asthma and decreased alveolar NO concentration toward normal in alveolitis. In conclusion, extended exhaled NO measurement can be used to separately assess alveolar and bronchial inflammation and to assess disease activity/severity in asthma and alveolitis.

n-3 Fatty acids and asthma

“…RCT cross-over design Three-arm comparison of fish oil v. evening primrose oil (n-6 group) v. olive oil using liquid oil supplementation 2-week run-in period followed by 30 (57) RCT, double-blind, cross-over, placebocontrolled trial 3-week supplementation period in each arm 2-week washout phase n-3: 3·2 g EPA and 2·0 g DHA Placebo: Matched capsules with olive oil 16 subjects Age 23 ± 1·6 years Participants with clinically treated mild-moderate asthma with a FEV 1 >70 % predicted Improved pulmonary function to below the diagnostic EIB threshold Reduction in medication usage Reduction in induced sputum differential cell count percentage and concentrations of LTC 4 -LTE 4 , PGD 2 , IL-1β and TNF-α before and following exercise on the n-3 fatty acid diet Significant reduction in LTB 4 and a significant increase in LTB 5 generation from activated polymorphonuclear cells on the n-3 fatty acid diet n-3 Fatty acids and asthma (126) RCT, double-blind, cross-over study Subjects entered the study on their normal diet, and then received either fish oil capsules or placebo n-3: 3·2 g EPA and 2·0 g of DHA Placebo: Matched capsules with olive oil 10 athletes and 10 controls Age (asthmatics 23·2 ± 1·9 years; controls 22·4 ± 1·7 years) Participants with clinically diagnosed EIB No effect on pre-exercise pulmonary function in either group Improved post-exercise pulmonary function Reduction in LTE 4 , 9α, 11β-PG F 2 , LTB 4 , TNF-α, and IL-1β, on the n-3 PUFA diet compared with baseline and placebo diets and after exercise challenge Studies reporting benefits of n-3 supplementation (in children)…”

Exhaled nitric oxide from lung periphery is increased in COPD

“…Recently, methods for measuring eNO at multiple expiratory flows (MEFeNO) [13,14] have been used to detect elevated levels of alveolar NO in fibrosing alveolitis [13], asthma [15,16] and COPD [17] leading to the refinement of analytical methods to discriminate exhaled NO sources in the lung [18].…”

Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox

“…The characteristics of NO gas exchange are unique compared with other endogenous gases because exhaled NO is thought to have a significant alveolar and airway source (6,8,15,22). A two-compartment model is commonly used to characterize NO exchange dynamics for healthy and diseased lungs (9,11,13,20,21,23,24,27,29), by partitioning exhaled NO into airway and alveolar contributions using three flow-independent NO exchange parameters: maximum flux of NO from the airways (JЈaw NO ), the diffusing capacity of NO in the airways (Daw NO ), and the steady-state alveolar concentration (CA NO ). However, the two-compartment model considers only convection of NO in the airways as a transport mechanism and has neglected axial diffusion of NO in the gas phase to preserve mathematical simplicity.…”