Minerva medica
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Inhaled corticosteroids are the cornerstone for the treatment of stable asthma, however, when disease severity increases, escalating therapy to combinations of drugs acting on distinct signalling pathways is required. It is advantageous to providing evidence of a synergistic interaction across drug combinations, as it allows optimizing bronchodilation while lowering the dose of single agents. In the respiratory pharmacology field, two statistical models are accepted as gold standard to characterize drug interactions, namely the Bliss Independence criterion and the Unified Theory. In this review, pharmacological interactions across drugs approved for the treatment of asthma have been systematically assessed. ⋯ There is still limited knowledge regarding the mechanistic basis underlying pharmacological interactions across drugs approved for asthma. The synergism elicited by combined agents is an effect of class. Specifically designed clinical trials are needed to confirm the results coming from preclinical evidence, but also to establish the minimal dose for combined agents to induce a synergistic interaction and maximize bronchodilation.
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Asthma has long been recognized as a chronic inflammatory disease of the airways, often in response to inhaled allergens prompting inappropriate activation of the immune response involving a range of cells including mast cells, Th2 lymphocytes and eosinophils alongside a wide range of inflammatory mediators. First-line therapy for treatment of persistent asthma involves the use of inhaled corticosteroids (ICS) in combination with inhaled β
2 -agonists enabling both the control of the underlying airways inflammation and a reduction of airway hyperresponsiveness. ⋯ The success of fixed dose combination inhalers containing both a bronchodilator and an anti-inflammatory drug has also led to the development of "bifunctional" drugs which are molecules specifically designed to have two distinct pharmacological actions based on distinct pharmacophores. In this review we will discuss these different pharmacological approaches under development for the treatment of bronchial asthma and the available preclinical and clinical data. -
Asthma is a very heterogeneous disease and since early childhood many classifications have been proposed according to phenotype and endotype. The phenotype includes the clinical features of asthma such as age of onset, triggers, comorbidities, response to treatment and evolution over time. ⋯ A deep knowledge of phenotype and endotype of the patient may guide a tailored therapeutic approach. In this review the main phenotypes and endotypes of asthma acknowledged in children will be discussed.