Both inflammation and remodeling influence nitric oxide output in children with refractory asthma

Mahut, Bruno; Delclaux, Christophe; Tillie‐Leblond, I.; Gosset, Philippe; Delacourt, Christophe; Zerah-Lancner, Françoise; Harf, Alain; Blic, J. de

doi:10.1016/j.jaci.2003.10.038

Cited by 86 publications

(82 citation statements)

References 17 publications

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“…Severe asthma with bronchial obstruction This phenotype of severe asthma is characterised in our study by a significant decrease in FEV1 (mean 82, range 78-86% pred) even if it remains within the accepted limits of normal, as in other studies in severe asthmatic children [22,23]. This finding is probably due to the fact that the normal value of FEV1 in children at school age is .90%, as in our cluster 3 in which the mean value of FEV1 was 97% pred (range 95-100% pred).…”

Section: Asthma With Severe Exacerbations and Multiple Allergiessupporting

confidence: 80%

Two novel, severe asthma phenotypes identified during childhood using a clustering approach

Just

Gouvis-Echraghi²,

Rouve³

et al. 2012

Eur Respir J

152

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Unsupervised cluster analysis has already been used to identify severe phenotypes of childhood asthma, but without taking into account inflammatory markers. The aim of this study was to define independent homogeneous phenotypic clusters of severe asthma in a cohort of asthmatic children.Cluster analysis was applied to 19 variables from 315 children enrolled in the Trousseau Asthma Program in Paris, France.Three independent clusters of asthma were identified. Cluster 1, asthma with severe exacerbations and multiple allergies: 103 children had more sensitisations to inhaled allergens and food allergens, more blood eosinophils and basophils, more uncontrolled asthma despite high doses of inhaled corticosteroid and more hospitalisations for exacerbation. Cluster 2, severe asthma with bronchial obstruction: 72 children were significantly older, had the highest body mass index, a lower forced expiratory volume in 1 s, more pronounced blood neutrophils and significantly higher levels of all classes of immunoglobulin (Ig), except IgE. Cluster 3, mild asthma: 140 children did not show statistically significant features.These results could lead to improved management of severe asthma in children by optimising treatment strategies, i.e. anti-allergic drugs, such as anti-IgE for children with the allergic phenotype, and anti-neutrophil drugs, such as macrolides for those with the obstructive phenotype.

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Section: Asthma With Severe Exacerbations and Multiple Allergiessupporting

confidence: 80%

Two novel, severe asthma phenotypes identified during childhood using a clustering approach

Just

Gouvis-Echraghi²,

Rouve³

et al. 2012

Eur Respir J

152

View full text Add to dashboard Cite

show abstract

“…As compared with other investigators who measured alveolar NO in adults with mildto-moderate persistent asthma [21], severe asthma [11], and in children with mild [22] and refractory asthma [10], the present authors obtained alveolar NO levels in a lower range (3-4-fold lower). This could be due to differences between patient characteristics and/or differences in the technical aspects of the measurements, such as the use of higher flow rates to calculate alveolar NO in the present study.…”

Section: Discussionsupporting

confidence: 53%

“…Alveolar NO has been related to bronchoalveolar lavage (BAL) eosinophil cationic protein levels in children [10] and to BAL eosinophil counts in adults [11]. However, the relationship between alveolar NO as a measure of peripheral airway inflammation and physiological tests of peripheral airway function has never been investigated.…”

mentioning

confidence: 99%

Alveolar nitric oxideversusmeasures of peripheral airway dysfunction in severe asthma

Veen¹,

Sterk²,

Schot³

et al. 2006

Eur Respir J

129

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Alveolar nitric oxide (NO) is a measure of peripheral airway inflammation in asthma, potentially associated with disease severity. The relationship between alveolar NO and physiological tests of peripheral airway (dys)function has not been investigated. The present authors hypothesised that peripheral airway inflammation and dysfunction are inter-related and associated with asthma severity.Alveolar NO was compared between 17 patients with mild-to-moderate asthma and 14 patients with severe asthma and related to total lung capacity (TLC), residual volume (RV)/TLC, thoracic gas volume (FRC), slope of the single breath nitrogen washout curve (dN 2 ), closing capacity (CC)/ TLC and fall in forced vital capacity at the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second. In patients with severe asthma, strong correlations were found between alveolar NO and RV/TLC % pred, FRC % pred, dN 2 , and CC/TLC. Patients with oral steroid-dependent asthma had higher alveolar NO levels (2.7 ppb) compared with the other patients with severe (0.6 ppb) and mild-to-moderate asthma (0.3 ppb).The present authors conclude that alveolar nitric oxide is closely related to parameters of peripheral airway dysfunction in patients with severe asthma, and that oral steroid-dependent asthmatics have more peripheral airway disease than nonsteroid-dependent asthmatics. This suggests that patients on chronic oral steroid treatment have more extensive disease and require additional anti-inflammatory treatment to better target the peripheral airways.

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“…27 The apparent discordance between oral and nasal FE NO and EBC pH in asthma and AD is probably a result of the different causes of modification of the 2 parameters. FE NO is principally a product of activated macrophages, eosinophils, and airway epithelial cells, 28 and the variation of pH is caused by a wide variety of inflammatory pathways. 29 Finally, the increased levels of nasal FE NO observed in patients with moderate asthma are related to a persistent inflammation in the upper airways, suggesting the need to use a nasal anti-inflammatory therapy in these subjects.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive methods for the detection of upper and lower airway inflammation in atopic children

Profita

Grutta²,

Carpagnano

et al. 2006

Journal of Allergy and Clinical Immunology

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Both inflammation and remodeling influence nitric oxide output in children with refractory asthma

Cited by 86 publications

References 17 publications

Two novel, severe asthma phenotypes identified during childhood using a clustering approach

Two novel, severe asthma phenotypes identified during childhood using a clustering approach

Alveolar nitric oxideversusmeasures of peripheral airway dysfunction in severe asthma

Noninvasive methods for the detection of upper and lower airway inflammation in atopic children

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