TY - JOUR
T1 - Bronchial nitric oxide flux (J′aw) is sensitive to oral corticosteroids in smokers with asthma
AU - Spears, Mark
AU - Weir, Christopher J.
AU - Smith, Andrew D.
AU - McSharry, Charles
AU - Chaudhuri, Rekha
AU - Johnson, Martin
AU - Cameron, Euan
AU - Thomson, Neil C.
N1 - Funding Information:
This study was supported by the donation of a Niox-Flex machine and educational grant from Aerocrine which covered servicing and maintenance. Aerocrine had no involvement in the study design, performance, analysis, interpretation of data and manuscript preparation. Greater Glasgow and Clyde Health board acted as sponsor for this study and Dr Mark Spears was the recipient of an academic training fellowship from the Chief Scientists Office (Scotland) during this period of research. The authors conceived, conducted, analysed, interpreted and prepared the submitted manuscript.
PY - 2011/12
Y1 - 2011/12
N2 - Background: Exhaled nitric oxide provides a convenient, non-invasive insight into airway inflammation. However it is suppressed by current smoking, reducing its potential as an endpoint in studies of smokers with asthma, a group with increased symptoms and poor clinical responses to corticosteroids. We examined extended nitric oxide analysis as some derived variables are thought to be unaffected. Therefore this approach could reveal hidden inflammation and enable its use as an exploratory endpoint in this group. Methods: Smokers (n = 22) and never smokers (n = 21) with asthma performed exhaled nitric oxide measurements and spirometry before and after two weeks of oral dexamethasone (6 mg/1.74 m 2/day). Linear and non-linear nitric oxide analysis was performed to derive estimates for alveolar nitric oxide (C alv) and nitric oxide flux (J′ aw) for each subject. Results: FE NO50 was significantly lower in smokers with asthma and did not change significantly in response to dexamethasone. C alv derived by linear modelling was lower in smokers with asthma and did not change significantly in response in either group. J′ aw was substantially lower in smokers with asthma (smokers (median (IQR)); 573 pl/s (217, 734), non-smoker; 1535 pl/s (785, 3496), p = 0.001) and was reduced in both groups following dexamethasone (non-smokers change (mean (95% CI)); -743.3 pl/s (-1710, -163), p = 0.005, smokers; -293 pl/s (-572, -60), p = 0.016). Correction for axial flow did not substantially change the derived results. Conclusions: Bronchial NO flux appears to be sensitive to oral dexamethasone and may provide a useful exploratory endpoint for the analysis of novel anti-inflammatory therapies in smokers with asthma.
AB - Background: Exhaled nitric oxide provides a convenient, non-invasive insight into airway inflammation. However it is suppressed by current smoking, reducing its potential as an endpoint in studies of smokers with asthma, a group with increased symptoms and poor clinical responses to corticosteroids. We examined extended nitric oxide analysis as some derived variables are thought to be unaffected. Therefore this approach could reveal hidden inflammation and enable its use as an exploratory endpoint in this group. Methods: Smokers (n = 22) and never smokers (n = 21) with asthma performed exhaled nitric oxide measurements and spirometry before and after two weeks of oral dexamethasone (6 mg/1.74 m 2/day). Linear and non-linear nitric oxide analysis was performed to derive estimates for alveolar nitric oxide (C alv) and nitric oxide flux (J′ aw) for each subject. Results: FE NO50 was significantly lower in smokers with asthma and did not change significantly in response to dexamethasone. C alv derived by linear modelling was lower in smokers with asthma and did not change significantly in response in either group. J′ aw was substantially lower in smokers with asthma (smokers (median (IQR)); 573 pl/s (217, 734), non-smoker; 1535 pl/s (785, 3496), p = 0.001) and was reduced in both groups following dexamethasone (non-smokers change (mean (95% CI)); -743.3 pl/s (-1710, -163), p = 0.005, smokers; -293 pl/s (-572, -60), p = 0.016). Correction for axial flow did not substantially change the derived results. Conclusions: Bronchial NO flux appears to be sensitive to oral dexamethasone and may provide a useful exploratory endpoint for the analysis of novel anti-inflammatory therapies in smokers with asthma.
KW - Alveolar nitric oxide
KW - Asthma
KW - Corticosteroid
KW - Nitric oxide flux
KW - Smoking
UR - http://www.scopus.com/inward/record.url?scp=81155159752&partnerID=8YFLogxK
U2 - 10.1016/j.rmed.2011.06.014
DO - 10.1016/j.rmed.2011.06.014
M3 - Article
C2 - 21840187
AN - SCOPUS:81155159752
SN - 0954-6111
VL - 105
SP - 1823
EP - 1830
JO - Respiratory Medicine
JF - Respiratory Medicine
IS - 12
ER -