Page 44 - Comprehensive treatment of patients with glucocorticoid-dependent severe asthma

Chapter 2
is that treatment with proton pump inhibitors is indicated only if the patient presents with clinical symptoms of gastro-esophageal reflux, but not in patients without symptoms. Whether the same recommendation applies to patients with severe refractory asthma requires further investigation.
Other proposed phenotypes of (severe) asthma and targeted therapies
An asthma phenotype that did not emerge from the cluster analyses is neutrophilic asthma. In this subtype of severe asthma, airway eosinophils are either absent or suppressed by treatment in the presence of a high level of asthma symptoms [174;175], while neutrophils [176] and IL-8 levels in the airways [177] are increased. Conventional therapies such as inhaled corticosteroids, although very effective in those with eosinophilic inflammation, have limited efficacy in neutrophilic asthma [178].
A proposed targeted therapy for the neutrophilic asthma phenotype is macrolide antibiotics [179]. Clarithromycin has been reported to decrease the neutrophil chemo-attractant Interleukin-8 in induced sputum in patients with neutrophilic asthma, even though insignificant against placebo, with a simultaneous improvement in asthma symptoms [179]. Thus, for patients with neutrophilic asthma, a trial of macrolide antibiotics might be a good choice.
Another potentially related phenotype of severe refractory asthma is the up-regulated tumor necrosis factor (TNF)-alpha phenotype, proposed by Berry and colleagues [180]. Because of the role of TNF in promoting sputum neutrophilia and airway hyperresponsiveness [181] anti-TNF monoclonal antibody seemed a good candidate for the treatment of this type of severe asthma [182;183]. Unfortunately the enthusiasm of the first results [180] was followed by disappointment and concern about the serious adverse events of the drug [184]. Consequently, this treatment is no longer considered an option in patients with severe asthma.
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