Asthma diagnosis and treatment
Severe asthma is associated with a loss of LX4, an endogenous anti-inflammatory compound

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Background

Lipoxins and 15-epi-lipoxins are lipid mediators that modulate leukocyte trafficking and promote the inflammation resolution. They are produced by different enzymatic pathways. Patients with severe asthma present ongoing airway inflammation despite chronic long-term treatment including oral glucocorticoids.

Objectives

The aim of this study was to assess the presence of proinflammatory and anti-inflammatory mediators in the supernatants of induced sputum.

Methods

Induced sputum supernatants were collected from 10 normal subjects; 12 subjects with mild, 15 with moderate, and 24 with severe asthma; and 13 patients with chronic obstructive pulmonary disease. First, we validated the measurements of IL-8, leukotriene B4, lipoxin A4, and 15-epi-lipoxin A4 in these samples. Then we measured these mediators by using immunoenzymatic methods.

Results

IL-8 levels were highly increased in patients with severe asthma (P < .0001), and leukotriene B4 levels were significantly increased in patients with severe asthma and patients with chronic obstructive pulmonary disease. Lipoxin A4 was significantly increased in the supernatant obtained from patients with mild asthma (P < .0001), whereas 15-epi-lipoxin A4 levels were higher in patients with severe asthma (P = .05). More interestingly, we found a positive correlation between the level of lipoxin A4 and IL-8 in patients with mild asthma.

Conclusion

These results indicate that induced sputum is a suitable method to assess lipoxin and 15-epi-lipoxin measurements in bronchi. The mechanisms involved in the synthesis of these 2 eicosanoid mediators would be helpful to understand better the imbalance between proinflammatory and anti-inflammatory mediators occurring in severe asthma. Lipoxin production involves interaction between lipoxygenases, whereas 15-epi-lipoxin production might involve CytP450 activity.

Section snippets

Patients

Subject characteristics are listed in Table I. Fifty-one subjects with asthma were selected according to the American Thoracic Society criteria.27 All had a reversible airway obstruction assessed by a 12% increase in FEV1 after inhalation of 200 μg salbutamol or a positive challenge with methacholine, with at least 20% fall in FEV1 and/or a 15% increase in FEV1 after a short course of oral glucocorticoids. The clinical severity of asthma was assessed according to GINA guidelines.28 Twelve

Patient characteristics

Demographic characteristics of all subjects are shown in Table I. Patients with severe asthma and COPD were older than patients with intermittent and moderate asthma and control subjects (P = .0002). Patients with intermittent asthma and COPD were not treated with steroids. FEV1 of all groups of subjects was significantly different (P < .001), and by using Bonferroni-Dunn posttest, significant differences were observed between all of the groups except patients with mild asthma versus controls and

Discussion

The current study demonstrates that patients with severe asthma present a persistent inflammation characterized by the proinflammatory IL-8 and LTB4 overproduction detected in supernatants of induced sputum. In the same way, we also observed that LTB4 was increased in supernatants of patients with COPD. Moreover, the anti-inflammatory LXA4 was present in supernatants of induced sputum and was increased in patients with mild asthma. Inversely, the anti-inflammatory LXA4 epimer, 15-epi-LXA4, was

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    Supported by CIFRE research grant #99679 and by a grant from the Direction de la Recherche Clinique of CHU of Montpellier (AOI 1995 UF7515).

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