Effects of Inhaled Steroids on Blood Eosinophils in Moderate Asthmaa

Laviolette, Michel; Ferland, Claudine; Trepanier, L A; Rocheleau, H.; Dakhama, Zzedine; Boulet, Louis‐Philippe

doi:10.1111/j.1749-6632.1994.tb39812.x

Cited by 13 publications

(5 citation statements)

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“…We previously showed that, in subjects with moderate asthma, a low dose of inhaled CS decreased both ionophore-induced LTC 4 release and the GM-CSF priming effect on this release [18]. In the present study, no effect of oral CS was observed on LTC 4 release to ionophore in subjects with severe asthma.…”

Section: Discussioncontrasting

confidence: 35%

“…In a double-blind crossover clinical trial, a low dose of inhaled CS reduced eosinophil ionophore-induced LTC 4 release and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhancement of this response in subjects with moderate asthma [18]. Furthermore, this diminished GM-CSF response observed with inhaled CS correlated with concomitant improvement in airway hyperreactivity as measured by methacholine challenge.…”

Section: Introductionmentioning

confidence: 99%

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Eosinophil Activation Status and Corticosteroid Responsiveness in Severe Asthma

Bossé¹,

Audette

Laflamme³

et al. 2000

Int Arch Allergy Immunol

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Background: Since eosinophils are implicated in asthma pathogenesis, we investigated whether these cells were activated in severe asthma. Methods: Twenty-six asthmatics with different clinical responses to oral corticosteroid (CS), i.e. sensitive [change in forced expiratory volume in 1 s (ΔFEV₁) ≥ 25% after oral methylprednisolone, 40 mg daily, for 14 days, n = 7], resistant (ΔFEV₁ ≤ 15%, n = 9) and dependent (≥ 20 mg oral prednisone daily for acceptable asthma control, n = 10), were studied. Results: Calcium ionophore-induced leukotriene (LT) C₄ release of purified blood eosinophils was similar in the three groups. Cell incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced ionophore-induced LTC₄ release, and this effect was higher in CS-sensitive (5-fold) than in CS-resistant subjects (1.7-fold) (p = 0.02). CS treatment decreased blood eosinophil counts in these two groups of subjects (p ≤ 0.02) and decreased GM-CSF-enhanced LTC₄ release in CS-sensitive asthmatics only (p = 0.04). In contrast, despite a high mean daily dose of oral CS (35 ± 8 mg), blood counts of eosinophils from CS-dependent subjects were higher (p = 0.03) and GM-CSF enhancement of LTC₄ release was greater (2.8-fold) than in CS-sensitive (2.1-fold) and CS-resistant (1.7-fold) subjects (p = 0.04). Interestingly, serum from CS-resistant subjects reduced GM-CSF enhancement of LTC₄ release by eosinophils of CS-sensitive asthmatics (p = 0.001). Conclusions: Eosinophils from CS-dependent asthmatics have an impaired response to CS, whereas serum from CS-resistant subjects contains an inhibitor of eosinophil response to GM-CSF.

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Section: Discussioncontrasting

confidence: 35%

Section: Introductionmentioning

confidence: 99%

Eosinophil Activation Status and Corticosteroid Responsiveness in Severe Asthma

Bossé¹,

Audette

Laflamme³

et al. 2000

Int Arch Allergy Immunol

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“…to assure adequate symptom control. The addition of inhaled steroid led to better control of their asthma and to a decrease in blood eosinophil count, LTC 4 production, and GM-CSF in vitro priming compared to a placebo [33]. We postulated that this effect was due to a reduced bronchial inflammation and release of proinflammatory mediators acting on blood eosinophils.…”

mentioning

confidence: 94%

“…However, to control their asthma symptoms, these subjects took high doses of inhaled steroids and oral steroids. As mentioned above, low doses of inhaled steroids decreased blood eosinophil LTC 4 production of asthmatics with symptomatic asthma [33]. Therefore, the combined high dose inhaled steroids and oral steroids probably modulated bronchial cytokine production more efficiently, and also acted directly on blood eosinophils following their systemic absorption, inhibiting, at least partly, their activation and normalizing the ionophore-induced LTC 4 release [41][42][43].…”

mentioning

confidence: 99%

Blood eosinophil leukotriene C4 production in asthma of different severities

Laviolette¹,

Ferland²,

Comtois³

et al. 1995

Eur Respir J

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In asthma, activation and recruitment of eosinophils to the bronchial mucosa amplifies many cellular functions. The blood eosinophil count and the number of hypodense eosinophils increase with asthma severity. Eosinophils produce numerous proinflammatory mediators in response to a variety of agonists, notably the peptido-leukotriene (LT) C4, a potent bronchoconstrictor. In this study, we have evaluated blood eosinophil LTC4 release and its modulation by cytokines in normal individuals and in subjects with asthma of various severities: mild (beta 2-agonist on demand); moderate (inhaled steroids on a regular basis); and severe (inhaled and oral steroids on a regular basis). Eosinophils were isolated using a modified Percoll gradient technique, which recovers both hypodense and normodense eosinophils in a global cell population. Eosinophils released detectable amounts of LTC4 only in the presence of the stimulus (calcium ionophore A23187, 2 microM). The ionophore-induced LTC4 release was greater in moderate asthmatics (mean +/- SEM 5.7 +/- 1.3 pg x 10(3)/250,000 eosinophils) than in normal individuals (1.6 +/- 0.4 pg x 10(3)/250,000 eosinophils), mild asthmatics (1.8 +/- 0.3 pg x 10(3)/250,000 eosinophils) and severe asthmatics (2.0 +/- 0.3 pg x 10(3)/250,000 eosinophils). Granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) amplified the ionophore-induced LTC4 release in the four groups from 1.9 to 2.6 and 1.9 to 2.8 fold, respectively. Interleukin-3 (IL-3) did not increase LTC4 production except by the eosinophils of the severe asthmatics whose ionophore-induced LTC4 production was enhanced by 1.9 fold. These data demonstrate that the asthmatic bronchial inflammatory process may modify blood eosinophil LTC4 release and its modulation by cytokines according to asthma severity and treatment.

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“…Eosinophils have been shown to be sensitive to the effects of gluticorticoids, because treatment with glucocorticoids has been shown to reduce the level of eosinophils in the peripheral blood (3,4) and airways of individuals with asthma (5), and to inhibit the allergeninduced increased levels of eosinophils in the peripheral blood and airways (6)(7)(8). The level of sputum eosinophils has been shown to predict the clinical benefit of steroid treatment for people with asthma (9,10).…”

mentioning

confidence: 99%

Increased Levels of Airway Neutrophils Reduces the Inhibitory Effects of Inhaled Glucocorticosteroids on Allergen‐Induced Airway Eosinophils

Gauvreau

Inman

Kelly

et al. 2002

Canadian Respiratory Journal

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BACKGROUND: Treatment with inhaled glucocorticosteroids attenuates allergen-induced airway inflammation but is less effective in people with asthma who have noneosinophilic airway inflammation. OBJECTIVE: Studies in which glucocorticosteroid treatment was used before allergen challenges were re-examined to determine whether the efficacy of steroid treatment could be predicted by baseline levels of sputum inflammatory cells. PATIENTS AND METHODS: Twenty-eight nonsmoking subjects with atopic asthma controlled by beta 2 -agonists participated in only one of three studies, each carried out with a double-blind, placebo controlled, randomized, crossover design. Subjects were treated with glucocorticosteroids or placebo for six to eight days and then underwent allergen inhalation challenge. Spirometry was measured for 7 h after allergen challenge, and then sputum inflammatory cells were measured. Sputum inflammatory cells were also measured before and after treatment, and 24 h after allergen challenge. The per cent inhibition of the allergeninduced airway responses by glucocorticosteroids was calculated. RESULTS: Inhaled gluticocorticosteroids significantly attenuated the early and late asthmatic responses, and the number of allergeninduced sputum eosinophils (P<0.05). There was a significant negative relationship between the number of sputum neutrophils at baseline, and the per cent inhibition of allergen-induced sputum eosinophils measured at 7 h (r=-0.61, P<0.001) and 24 h (r=-0.73, P<0.0001) after challenge, suggesting that glucocorticosteroids are less effective in attenuating allergen-induced airway inflammation in subjects with high levels of neutrophils. There was no correlation between the number of sputum eosinophils at baseline and the per cent inhibition of allergen-induced responses. CONCLUSIONS: Baseline airway neutrophils, not eosinophils, can be used to predict the efficacy of inhaled steroids on allergeninduced sputum eosinophils. Key Words: Airway inflammation; Allergen inhalation; Eosinophils; Glucocorticosteroids; Neutrophils; Sputum induction Résumé à la page suivanteA sthma is well recognized as an inflammatory disorder of the airways characterized by increased levels of eosinophils (1,2). Eosinophils have been shown to be sensitive to the effects of gluticorticoids, because treatment with glucocorticoids has been shown to reduce the level of eosinophils in the peripheral blood (3,4) and airways of individuals with asthma (5), and to inhibit the allergeninduced increased levels of eosinophils in the peripheral blood and airways (6-8). The level of sputum eosinophils has been shown to predict the clinical benefit of steroid treatment for people with asthma (9,10).Although eosinophils are considered to be the hallmark of asthmatic airway inflammation, there is increasing evidence that neutrophils may also play a prominent role. Elevated levels of neutrophils have been measured in the airways of subjects with stable asthma (11), during exacerbations of asthma (12) and in fatal asthma of sudden onset ...

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Effects of Inhaled Steroids on Blood Eosinophils in Moderate Asthmaa

Cited by 13 publications

References 0 publications

Eosinophil Activation Status and Corticosteroid Responsiveness in Severe Asthma

Eosinophil Activation Status and Corticosteroid Responsiveness in Severe Asthma

Blood eosinophil leukotriene C4 production in asthma of different severities

Increased Levels of Airway Neutrophils Reduces the Inhibitory Effects of Inhaled Glucocorticosteroids on Allergen‐Induced Airway Eosinophils

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