ArticlesManagement of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial
Introduction
Asthma is a complex respiratory disorder that is characterised by variable and recurring symptoms, airflow obstruction, and underlying airway inflammation. In 2007, the US National Heart, Lung and Blood Institute (NHLBI) updated its Guidelines for the Diagnosis and Management of Asthma,1, 2 and proposed that treatment to achieve asthma control should aim both to regulate the manifestations of impairment (ie, symptoms, need for rescue treatment, limitations of activity, and pulmonary function) and to reduce future risk.
Asthma symptoms and exacerbations are theoretically linked to underlying inflammation of airways, but are not direct indicators of inflammation. Measurement of biomarkers that are more closely associated with airway inflammation could improve asthma control by enabling treatment to be better directed. One such marker of airway inflammation is the fraction of exhaled nitric oxide (NO),3 which has been shown to increase during periods of uncontrolled asthma4, 5, 6, 7, 8, 9, 10, 11, 12 and decrease during treatment with anti-inflammatory agents.13, 14, 15, 16, 17, 18, 19, 20, 21 Previous trials have assessed the use of fraction of exhaled NO as an alternative to conventional modification of treatment based on symptoms and pulmonary function.22, 23, 24, 25 However, in practice, clinicians would be more likely to monitor exhaled NO as an additional way to monitor airway inflammation, rather than as a replacement. Therefore, we believe that a clinically more relevant question is whether the addition of NO monitoring to guideline-based management can improve management of asthma. We aimed to assess the effectiveness of measurement of fraction of exhaled NO as an adjunct to guideline-directed management of asthma in a population of inner-city adolescents and young adults who were characterised by high levels of atopy, allergen exposure, and poor asthma control.26, 27, 28, 29, 30
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Participants
We designed a randomised, double-blind, parallel-group trial at ten centres in cities across the USA. We initially screened participants on the basis of census tracts. Each census tract had between 2500 and 8000 people and was designed to be homogeneous with respect to population characteristics, economic status, and living conditions. We restricted eligibility to residents of urban census tracts in which at least 20% of households had incomes below the federal poverty threshold. Eligible
Results
Between September, 2004, and December, 2005, we screened 780 patients and excluded 234 who refused consent, did not adhere to treatment during the run-in period, or were active smokers (figure 1). The mean age of the 546 patients who were enrolled and randomly assigned was 14·4 years (IQR 13–16). At enrolment, 422 (77%) of the 546 participants did not have good control of their asthma symptoms (control level >1). 313 (57%) of the 546 participants were assessed to have control levels of 3 or 4,
Discussion
We sought to determine whether measurement of fraction of exhaled NO added value to commonly used control measures for asthma treatment based on national guidelines.1, 2 Whereas other studies on fraction of exhaled NO have typically replaced usual measures of symptoms and pulmonary function with NO as the basis for determining asthma treatment, we aimed to assess its use in combination with standard symptom-based approaches to treatment. We showed that use of current guidelines for asthma
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