New Drugs for Pediatric Asthma

Abstract

Asthma is the most common chronic disease in children. As suggested by international guidelines, the main goals of asthma treatment are symptoms control and lung function preservation, through a stepwise and control-based approach. The first line therapy based on inhaled corticosteroids may fail to reach control in more than one third of patients, especially adolescents, and in these lung function and quality of life may progressively worsen. Treatment with omalizumab, the first anti-immunoglobulin E recombinant humanized monoclonal antibody, has been definitely approved in pediatric uncontrolled asthma. In this review, we discuss the mechanisms and potential roles of emerging therapies for pediatric severe asthma. Novel biologic drugs (i.e., dupilumab, mepolizumab, reslizumab, and benralizumab) seem to be promising in reducing annual exacerbation rates and steroid-use in glucocorticoid-dependent cases, but available data are few and limited to adolescents and adults. Evidences on the use of the muscarinic antagonist tiotropium as controller medication in pediatric settings are progressively growing, sustaining an application as asthma maintenance treatment in children aged >6 years and in preschool children with persistent asthmatic symptoms, but well powered trials are needed to confirm its safety and efficacy. New inhaled corticosteroids (i.e., ciclesonide and mometasone) are effective as once-daily controller therapy, but long-term studies in the different pediatric ages are needed to compare effectiveness and safety to usual treatments. At present, the role of macrolides in pediatric severe asthma is controversial and their administration is not recommended routinely, but may be considered in children with neutrophilic asthma for reducing daily oral steroids administration and improving lung function. Despite the availability of several novel therapeutic strategies for uncontrolled asthma, future trials targeted at specific pediatric age subgroups are needed to support evidences of safety and efficacy also in children.

The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-Dependent YAP Pathway

“…The antiasthma medication ciclesonide is a GC used to treat asthma and allergic rhinitis. This new inhaled corticosteroid is effective as a once-daily controller therapy for pediatric asthma and reduces airway inflammation through once-daily administration [ 12 ]. Ciclesonide has strong anti-inflammatory activity in vitro and in vivo.…”

The FDA-Approved Anti-Asthma Medicine Ciclesonide Inhibits Lung Cancer Stem Cells through Hedgehog Signaling-Mediated SOX2 Regulation

“…Ciclesonide, a new inhaled corticosteroid, reduces airway inflammation through a single daily administration and controls asthma in atopic children [23]. Ciclesonide and budesonide inhibit the Hedgehog signaling pathway [25].…”

“…The anti-asthma medicine ciclesonide is a glucocorticoid (GC) used to treat asthma and allergic rhinitis. Ciclesonide, a new inhaled corticosteroid, is effective as a once-daily controller therapy for pediatric asthma and reduces airway inflammation through a single daily administration [23]. Ciclesonide has strong anti-inflammatory activity in vitro and in vivo.…”

The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-dependent YAP Pathway

“…YAP acts as a major inducer of CSC formation by upregulating SOX2 and SOX9 [30,31] Ciclesonide, a synthetic GC, decreases airway inflammation and controls asthma [12]. Ciclesonide binds efflux transporters, p-glycoprotein and breast cancer resistance protein (BCRP) and inhibits efflux [32].…”

“…The antiasthma medication ciclesonide is a synthetic GC drug for treating mild-to-severe asthma. This inhaled ciclesonide is effective for asthma and reduces airway inflammation [12]. The ligandingbinding affinity of ciclesonide to the GR is very higher than DEX [13].…”