Abstract
Whether exhaled NO helps to identify a specific phenotype of asthmatic patients remains debated. Our aims were to evaluate whether exhaled NO (FENO0.05) is independently associated (1) with underlying pathophysiological characteristics of asthma such as airway tone (bronchodilator response) and airway inflammation (inhaled corticosteroid [ICS]-dependant inflammation), and (2) with clinical phenotypes of asthma.We performed multivariate (exhaled NO as dependent variable) and k-means cluster analyses in a population of 169 asthmatic children (age ± SD: 10.5 ± 2.6 years) recruited in a monocenter cohort that was characterized in a cross-sectional design using 28 parameters describing potentially different asthma domains: atopy, environment (tobacco), control, exacerbations, treatment (inhaled corticosteroid and long-acting bronchodilator agonist), and lung function (airway architecture and tone).Two subject-related characteristics (height and atopy) and two disease-related characteristics (bronchodilator response and ICS dose > 200 μg/d) explained 36% of exhaled NO variance. Nine domains were isolated using principal component analysis. Four clusters were further identified: cluster 1 (47%): boys, unexposed to tobacco, with well-controlled asthma; cluster 2 (26%): girls, unexposed to tobacco, with well-controlled asthma; cluster 3 (6%): girls or boys, unexposed to tobacco, with uncontrolled asthma associated with increased airway tone, and cluster 4 (21%): girls or boys, exposed to parental smoking, with small airway to lung size ratio and uncontrolled asthma. FENO0.05 was not different in these four clusters.In conclusion, FENO0.05 is independently linked to two pathophysiological characteristics of asthma (ICS-dependant inflammation and bronchomotor tone) but does not help to identify a clinically relevant phenotype of asthmatic children.
Highlights
Numerous studies have evaluated exhaled nitric oxide (NO) correlates in asthma
Levels of asthma control were systematically assessed using only two levels of GINA guidelines during past three months:[11] controlled versus partially/ uncontrolled asthma
Patients and criteria of selection from the cohort We selected a sample of children, meeting the criteria of clinical and functional[13] diagnosis of asthma and who satisfied a full description of their asthma: these 28 variables are categorized as (1) anthropometrics, (2) past history, (3) parental smoking, level of control, treatment, and (3) pulmonary function
Summary
Numerous studies have evaluated exhaled nitric oxide (NO) correlates in asthma. We and others have emphasized that FENO is linked to other intrinsic dimensions of asthma such as airway reactivity/tone [2,3] and remodeling of airways[1,4]. All these relationships may explain the complex and still debated relationship between exhaled NO and asthma control/severity[4,5,6]. Extrinsic factors affect FENO such as tobacco exposure and asthma treatment[6,7].
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