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Efficacy and safety of phosphodiesterase 4 inhibitors in patients with asthma: A systematic review and meta‐analysis
Author(s) -
Luo Jian,
Yang Ling,
Yang Jing,
Yang Dan,
Liu BiCui,
Liu Dan,
Liang BinMiao,
Liu ChunTao
Publication year - 2018
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/resp.13276
Subject(s) - medicine , asthma , roflumilast , adverse effect , meta analysis , placebo , methacholine , odds ratio , fluticasone propionate , nausea , pulmonary function testing , randomized controlled trial , respiratory disease , lung , copd , pathology , alternative medicine
Phosphodiesterase 4 (PDE4) inhibitors are a novel medication approved for airway inflammatory diseases including chronic obstructive pulmonary disease. Their role and application in asthma are controversial and not defined. A comprehensive search was performed in major databases (1946–2016) using the keywords: ‘phosphodiesterase 4 inhibitor’ or ‘roflumilast’ and ‘asthma’. Placebo‐controlled trials reporting lung function, airway hyperresponsiveness by direct challenge, asthma control and exacerbations, and adverse events were included. Random or fixed‐effects models were used to calculate odds ratios (OR) and mean differences between the two treatment groups. Statistical analyses were conducted using Mann–Whitney U‐tests and Cochrane systematic review software, Review Manager. Seventeen studies were included in the systematic review, of which 14 studies were included in the meta‐analysis. Except for significant statistical heterogeneity in pre‐ and post‐challenge predicted percentage of forced expiratory volume in 1 s (FEV 1 %; I 2 = 72%, χ 2 = 3.35, P = 0.06), there was no heterogeneity in outcome measures. Roflumilast (500 μg) significantly improved FEV 1 (mean difference: 0.05, 95% CI: 0.01–0.09, Z = 2.50, P = 0.01), peak expiratory flow, asthma control and exacerbations, but showed variable effects on airway responsiveness to methacholine and a 20% fall in FEV 1 .Of note, PDE4 inhibitors were accompanied with significantly higher adverse events such as headache (OR: 3.99, 95% CI: 1.65–9.66, Z = 3.07, P = 0.002) and nausea (OR: 5.53, 95% CI: 1.38–22.17, Z = 2.41, P = 0.02). In patients with mild asthma, oral PDE4 inhibitors can be considered as an alternative treatment to regular bronchodilators and inhaled controllers.