Effect Of Roflumilast On Asthma Control In Moderate and Severe Asthma Patients

Белоглазов, В. А.; Popenko, Yuri; DuBuske, L.M.

doi:10.1016/j.jaci.2013.12.035

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“…65 Addition of roflumilast (500 mg) to high-dose fluticasone (500–1000 µg/day) for a month in patients with uncontrolled severe asthma better improved asthma than high-dose fluticasone alone possibly through affecting the neutrophilic component of the disease. 68 In OVA-sensitized and -challenged mice, roflumilast (5 mg/kg/day for 10 days orally) non-significantly decreased AHR but significantly reduced eosinophils, chronic inflammatory cells, subepithelial fibrosis, and thickening of the airway epithelium. Thus, roflumilast is an effective inhibitor of airway inflammation and remodeling.…”

Section: Discussionmentioning

confidence: 93%

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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Section: Discussionmentioning

confidence: 93%