ntroduction: The treatment of uncontrolled asthma has improved because of triple therapy that includes a long-acting muscarinic antagonist (LAMA) and biological drugs, but several patients are resistant to corticosteroids and/or cannot achieve adequate asthma control using such therapies. Areas covered: Herein, the authors review the current and emerging synthetic pharmacotherapy for uncontrolled asthma to overcome obstacles and limitations of biological therapies. The authors also provide their expert perspectives and opinion on the treatment of uncontrolled asthma. Expert opinion: LAMAs should be added to inhaled corticosteroid/long-acting β2-agonist combinations much earlier than currently recommended by the Global Initiative for Asthma strategy because they can influence the course of small airways disease, reducing lung hyperinflation and improving asthma control. Biological therapies are a major advance in the treatment of severe asthma, but their use is still very limited for several reasons. An alternative to overcome the use of biological therapies is to synthesize compounds that target inflammation-signaling pathways. Several pathways have been identified as potential targets to design either therapeutic or prophylactic drugs against asthma. Some new compounds have already been tested in humans, but results have often been disappointing probably because existing phenotypic and endotypic variants may unpredictably limit the therapeutic value of blocking a specific pathway in most asthmatics, although there may be a substantial benefit for a subgroup of patients.
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