Introduction: The enzyme, inducible nitric oxide synthase (iNOS), is upregulated in the airway epithelium in patients with allergic asthma resulting increased nitric oxide production. The concentration of nitric oxide in exhaled air (FENO) correlates with the degree of eosinophilic airway inflammation and has been proposed as a new breath test to assist in the management of asthma.
Key Aims: To determine the predictive accuracy of FENO compared with conventional testing in the diagnosis of asthma.
To assess the performance characteristics of FENO to predict steroid responsiveness compared with the conventional approach in patients presenting with non-specific respiratory symptoms.
To assess the role of FENO compared with conventional guidelines-based approach as a guide to adjusting inhaled corticosteroid therapy in patients with chronic persistent asthma.
Methods: Consecutive patients referred with chronic undiagnosed respiratory symptoms were enrolled. Comparisons were made between FENO, induced sputum analysis and other conventional tests (including peak flow variation, spirometry, response to oral steroid challenge) for predicting the presence of asthma in the first study, and for predicting response to four weeks inhaled fluticasone treatment in the second study.
In the third study, 110 subjects with chronic persistent asthma were enrolled into a single-blind placebo-controlled study during which subjects were randomly allocated to have their corticosteroid (fluticasone) dose adjusted on the basis of either FENO measurements or an algorithm based on conventional guidelines. The main outcomes were the frequency of asthma exacerbations and the mean daily dose of inhaled corticosteroid.
Results: In the first study, 17 of 47 consecutive patients were diagnosed with asthma. Sensitivities for the conventional tests (0-47%) were lower than for FENO (88%) and sputum eosinophils (86%), with overall significantly greater diagnostic accuracy for FENO and sputum eosinophils.
Fifty-two consecutive subjects completed the second study. When compared to the conventional tests, the predictive powers for FENO were consistently greater than for almost all other baseline measurements used to predict steroid responsiveness, with an optimum cut point of 47 ppb.
In the third study, the exacerbation rates were 0.49 (95% C.I. 0.20, 0.78) per patient per year in the FENO group and 0.90 (95% C.I. 0.31, 1.49) in the control group, representing a nonsignificant reduction of 45.6 percent (95% C.I. -78.5, 54.5%) in the FENO group. The final mean daily doses of fluticasone were significantly lower in for the FENO group compared with the conventional group (370 [mu]g/day (95% C.I. 263, 477) vs 641 [mu]g/day (95% C.I. 526, 756) respectively; p=0.003). There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).
Conclusions: FENO is comparable to induced sputum analysis and superior to the conventional methods currently used including peak flows and spirometry as a dignositic for asthma and as a predictor of steroid responsiveness in patients with chronic respiratory symptoms. FENO measurements as a guide to adjusting inhaled corticosteroid therapy compared to the conventional guidelines based approach results in significantly lower maintenance doses being achieved without compromising asthma control. The results of this thesis provide evidence to support the use of FENO measurements in routine clinical practice as a tool to improve the overall management and diagnosis of asthma.
| Identifer | oai:union.ndltd.org:ADTP/217754 |
| Date | January 2007 |
| Creators | Smith, Andrew D, n/a |
| Publisher | University of Otago. Dunedin School of Medicine |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://policy01.otago.ac.nz/policies/FMPro?-db=policies.fm&-format=viewpolicy.html&-lay=viewpolicy&-sortfield=Title&Type=Academic&-recid=33025&-find), Copyright Andrew D Smith |
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