Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats

Vanacker, Nele J.; Palmans, Els; Pauwels, Romain; Kips, Johan

doi:10.1183/09031936.02.02562001

Cited by 25 publications

(24 citation statements)

References 32 publications

(36 reference statements)

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“…This finding is consistent with previous reports in which ICS treatment reduced AHR when assessments were made immediately following exposure to allergen in both animals [21,37] and humans [29][30][31]. Furthermore, the present authors reported that inhibition of immune-mediated events attenuates AHR [32][33][34].…”

Section: Discussionsupporting

confidence: 83%

Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice

Southam¹,

Ellis²,

Wattie³

et al. 2008

European Respiratory Journal

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Despite the effectiveness of corticosteroids at resolving airway inflammation, they are only moderately effective at attenuating airway hyperresponsiveness (AHR). The extent to which corticosteroids are able to reverse or inhibit the development of sustained AHR is not known. The present study aimed to determine whether budesonide can resolve and or prevent the development of sustained AHR in mice.Mice were chronically exposed to allergen and treated with budesonide either: 1) briefly during the final weeks of exposure to allergen; 2) prolonged concurrently throughout exposure to allergen; or 3) delayed following final exposure to allergen. AHR was assessed 24 h (brief treatment) or 4 weeks (prolonged concurrent and delayed treatments) following final exposure to allergen.Brief budesonide intervention significantly attenuated the inflammation-associated AHR assessed immediately following final exposure to allergen. Similarly, prolonged concurrent budesonide treatment prevented the development of sustained AHR. Delayed budesonide intervention, however, did not resolve sustained AHR.In conclusion, the early introduction and, importantly, the persistence of corticosteroid treatment prevented the development of sustained airway hyperresponsiveness; however, the inability of corticosteroids to reverse established airway dysfunction indicates a limitation in their use for the complete, long-term management of airway hyperresponsiveness.

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Section: Discussionsupporting

confidence: 83%

Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice

Southam¹,

Ellis²,

Wattie³

et al. 2008

European Respiratory Journal

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“…41 to attenuate airway remodeling and AHR noted with longer treatment. 31 The observations by Sont et al 30 and Ward et al, 31 as well as others (Table I) [32][33][34][35][36][37][38][44][45][46] suggest that the corticosteroid dose and its duration of administration are important considerations when evaluating the effects of treatment on remodeling. These studies also suggest that some aspects of remodeling might be reversible and that current treatment end points (ie, symptoms alone) might not be fully informative on what approaches are needed to modify airway remodeling.…”

Section: Reticular Basement Membrane Thickeningmentioning

confidence: 90%

What effect does asthma treatment have on airway remodeling? Current perspectives

Durrani

Viswanathan

Busse

2011

Journal of Allergy and Clinical Immunology

151

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“…These results agree with previous studies. 41,[49][50][51][52] In the current study, the monotherapies showed modest non-significant decreases in AHR, while the combination groups showed significant decreases in AHR at MCh concentrations of 25 and 50 (mg/ml). These two doses of MCh could be clinically relevant because maximum doses of 16, 25, and 32 mg/ml are commonly used in various pulmonary functions testing laboratories.…”

Section: Discussionmentioning

confidence: 82%

Co-inhalation of roflumilast, rather than formoterol, with fluticasone more effectively improves asthma in asthmatic mice

Murad

Habıb

Rafeeq

et al. 2017

Exp Biol Med (Maywood)

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Impact statementRoflumilast, a selective phosphodiesterase-4 inhibitor, was approved for the treatment of chronic obstructive pulmonary disease (COPD). This study showed that co-inhalation of roflumilast and fluticasone significantly decreased airway hyperresponsiveness in ovalumin-asthmatic mice. Also, it more significantly improved inflammation and histopathological changes than co-inhalation of formoterol and fluticasone. The current results showed that inhaled roflumilast reduced counts of eosinophils, neutrophils, and macrophages in bronchoalveolar lavage fluid. Consequently, inhaled roflumilast might be of potential off-label benefit in treatment of eosinophilic and neutrophilic asthma and asthma-COPD overlap syndrome (ACOS). These results could also support other experimental and clinical studies addressing the same issue. AbstractRoflumilast is approved as an add-on therapy for chronic obstructive pulmonary disease. The inflammation in chronic obstructive pulmonary disease is mainly neutrophilic, while in asthma it is mainly eosinophilic, studies addressing role of roflumilast in eosinophilic inflammation are recommended. Also in severe asthma, the dominant inflammatory cells are neutrophils. Thus, roflumilast has a potential off-label use in the treatment of asthma. This study was designed to evaluate the effects of co-inhalation of roflumilast and fluticasone compared to that of formoterol and fluticasone in ovalbumin-sensitized and-challenged BALB/c mice. Besides normal control group, the ovalbumin-asthmatic mice were randomly divided into seven groups (n ¼ 8): positive control, vehicle-treated, and five drug-treated groups. Treatments (mg/kg) were given as 15 min-inhalation once/day for five days as follows: roflumilast (500), formoterol (50), fluticasone (1000), roflumilast þ fluticasone (500 þ 1000), and formoterol þ fluticasone (50 þ 1000). Penh values were measured in conscious unrestrained mice using the single-chamber whole-body plethysmography. Airway hyperreactivity to inhaled methacholine was evaluated. Bronchoalveolar lavage fluid was used for the measurements of levels of IL-4, IL-5, TNF-a, OVA-specific IgE, and total and differential white cells. Lung sections were stained with hematoxylin and eosin and periodic acid-Schiff. The asthmatic mice showed significant increases in airway hyperreactivity which were significantly reversed by the combination treatments. The asthmatic mice showed significant increases in levels of IL-4, IL-5, TNF-a, ovalbumin-specific IgE, and total and differential white cells in bronchoalveolar lavage fluid. All treatments (except formoterol) significantly reversed these changes mainly with roflumilast þ fluticasone. The asthmatic mice showed severe inflammatory infiltration and goblet cell hyperplasia which were maximally reversed by roflumilast þ fluticasone, while minimally reversed by formoterol. In conclusion, co-inhalation of roflumilast þ fluticasone more significantly improved inflammation and histopathological changes than co-inhalation of formoterol þ f...

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Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats

Cited by 25 publications

References 32 publications

Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice

Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice

What effect does asthma treatment have on airway remodeling? Current perspectives

Co-inhalation of roflumilast, rather than formoterol, with fluticasone more effectively improves asthma in asthmatic mice

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