Predicted versus absolute values in the application of exhaled nitric oxide measurements.

BACKGROUND: Constitutional factors such as age, sex and height, and acquired factors such as atopy and smoking, influence exhaled nitric oxide (F(E)NO) levels. The utility of predicted values based on reference equations which account for these factors has not been evaluated. AIM: To compare the performance characteristics of absolute versus % predicted values for F(E)NO as predictors of diagnosed asthma and steroid response. METHODS: We compared the sensitivities, specificities and likelihood ratios using F(E)NO (% predicted) with absolute values for F(E)NO (ppb) in 52 steroid-naive subjects with non-specific respiratory symptoms. The reference equations of Olin et al. (Chest, 2007) and Dressel et al. (Resp. Med., 2008) were used to derive predicted values. Receiver operating curve analyses were performed and the areas under the curve (AUC) were calculated for two outcomes: diagnosed asthma (yes/no), and steroid response after fluticasone for 4 weeks (defined as ≥ 12% increase in FEV(1); increase in mean morning PEF ≥ 15%; reduction in symptoms ≥ 1 point; increase in PC(20)AMP of ≥ 2 doubling doses). RESULTS: The AUCs for diagnosed asthma were: F(E)NO (absolute) 0.770; F(E)NO (% pred.): 0.758 (Olin) and 0.775 (Dressel) (NS). The AUCs for F(E)NO (abs.) and F(E)NO (% pred.) with respect to the four indices of steroid response were likewise not significantly different. CONCLUSION: Correcting F(E)NO for combinations of age, sex, height, smoking and atopy using reference equations did not enhance the performance characteristics of F(E)NO as a predictor of either the diagnosis of asthma or steroid responsiveness in patients with chronic airways-related symptoms.

Exhaled nitric oxide: a predictor of steroid response.

RATIONALE: The initial management of patients who present with persistent respiratory symptoms includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a "trial of steroid" to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements. OBJECTIVES: We aimed to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed-sequence, placebo-controlled trial of inhaled fluticasone for 4 weeks. METHODS: Comparisons of predictive accuracy were made between FENO and other conventional predictors: peak flows, spirometry, bronchodilator response, and airway hyperresponsiveness measured at baseline. "Steroid response" was defined as change in symptoms, peak flows, spirometry, or airway hyperresponsiveness to adenosine based on established guidelines and recommendations. RESULTS: Steroid response was significantly greater in the highest FENO tertile (> 47 ppb) for each endpoint. This outcome was independent of the diagnostic label. The predictive values for FENO were significantly greater than for almost all other baseline predictors, with an optimum cut point of 47 ppb. CONCLUSIONS: FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms. Assessing airway inflammation is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled antiinflammatory therapy.

Effects of terbutaline and budesonide on sputum cells and bronchial hyperresponsiveness in asthma.

Previous studies have shown that the regular administration of short acting beta-agonists can be associated with adverse effects on airway caliber and bronchial hyperresponsiveness (BHR) and that this may occur through a proinflammatory mechanism. The aim was to explore possible adverse effects of high-dose beta-agonist therapy and to assess any adverse interaction with corticosteroids. We undertook a randomized, crossover study to investigate the effects of 6 wk of treatment with regular terbutaline (1 mg four times a day), regular budesonide (400 microg twice a day), combined treatment, and placebo in subjects with mild to moderate asthma. Major endpoints were PD(15) saline, PD(20) methacholine, and induced sputum differential cell counts. Thirty-four subjects were randomized and 28 completed the study. PD(15) saline decreased on terbutaline alone compared with placebo treatment and on combined treatment compared with budesonide alone (mean fold decrease of 0.57 [95% CI = 0.36, 0.90] and 0.65 [95% CI = 0.43, 0.97], respectively). PD(20) methacholine was not affected by the use of terbutaline either alone or in combination with budesonide. The percentage of eosinophils in induced sputum increased during terbutaline treatment alone compared with placebo (median 8.3% versus 4.4%, p = 0.049). The addition of terbutaline to budesonide did not affect the percentage of eosinophils compared with budesonide treatment alone. These findings support the hypothesis that short-acting beta-agonists have a permissive effect on airway inflammation and that when used in high dose there may be an unfavorable interaction with inhaled corticosteroids.