Page 42 - Comprehensive treatment of patients with glucocorticoid-dependent severe asthma

Chapter 2
Remarkably, patients with severe asthma, chronic rhinosinusitis and nasal polyposis are also prone to inflammation and narrowing of the distal airways [114;115], resulting in air trapping and hyperinflation [111;131], which has been shown to be associated with more severe asthma, hospitalizations and ICU admissions [132].
Small airways inflammation can be targeted with ultrafine ICS, which have been shown to decrease the number of eosinophils in biopsies taken from the distal airways [133] reduce the number of asthma exacerbations [134] as well as the need for oral corticosteroids in patients with severe, refractory asthma.
The most important marker of disease severity in patients with the adult onset non-atopic asthma phenotype is persistent airway eosinophilia [116]. Persistent eosinophilia has been associated with frequent asthma exacerbations [135], fixed airflow limitation [136] more intubations [137] and many patients require continuous systemic corticosteroid treatment to keep their asthma under control [138;139]. Unfortunately the chronic use of oral corticosteroids is associated with serious side effects such as osteoporosis, diabetes, hypertension, cataract formation, and myophathy [140] and since these adverse effects are dose and time dependent all efforts should be taken to taper the oral corticosteroid to the lowest effective dose in each patient [141].
Steroid sparing drugs such as methotrexate [142], cyclosporine [143], Troleandomycin [144] and oral gold [145] have been applied in patients with prednisone-dependent asthma, but unfortunately none of these drugs has gained complete acceptance in clinical practice, because of either limited efficacy or unacceptable side effects [146;147].
A novel promising strategy to treat patients with persistent eosinophilic inflammation is to target the eosinophil itself. The anti IL-5 humanised monoclonal antibody mepolizumab has been demonstrated to be very efficacious in reducing the circulating eosinophils [148] and preventing eosinophil recruitment into the airways after allergen challenge [149]. In clinical trials, anti-IL5 significantly reduced the occurrence of induced [150] and spontaneous [151] asthma exacerbations in patients with persistent eosinophils in sputum. Mepolizumab treatment was also associated with
40