Abstract
In asthmatic adults, monoclonals directed against Type 2 airway inflammation have led to major improvements in quality of life, reductions in asthma attacks and less need for oral corticosteroids. The paediatric evidence base has lagged behind. All monoclonals currently available for children are anti-eosinophilic, directed against the T helper (TH2) pathway. However, in children and in low and middle income settings, eosinophils may have important beneficial immunological actions. Furthermore, there is evidence that paediatric severe asthma may not be TH2 driven, phenotypes may be less stable than in adults, and adult biomarkers may be less useful. Children being evaluated for biologicals should undergo a protocolised assessment, because most paediatric asthma can be controlled with low dose inhaled corticosteroid if taken properly and regularly. For those with severe therapy resistant asthma, and refractory asthma which cannot be addressed, the two options if they have TH2 inflammation are omalizumab and mepolizumab. There is good evidence of efficacy for omalizumab, particularly in those with multiple asthma attacks, but only paediatric safety, not efficacy, data for mepolizumab. There is an urgent need for efficacy data in children, as well as data on biomarkers to guide therapy, if the right children are to be treated with these powerful new therapies.
Highlights
The purpose of this review is to give a clinically focused update on the approach to the child with asthma for whom the prescription of a biologic is being considered, in order to appropriately select those children who need these expensive and invasive medications, to highlight the important differences between adult and paediatric severe asthma with regard to the use of biologicals and to summarise the paediatric biologic data currently published.The Lancet asthma commission has highlighted that the word “asthma” is an umbrella term comprising numerous endotypes [1]
This is relevant to the obese child with asthma, who may have T-helper 2 (TH2)-driven airway inflammation [46], but this is not invariable [47], and may have symptoms related to dysanaptic airway growth, defined as a normal first second forced expired volume (FEV1), a raised forced vital capacity (FVC) and a low FEV1/FVC ratio [48] or secondary to systemic inflammation driven by IL6 [49]
Paediatric STRA is often eosinophilic, but frequently, there is no evidence that the TH2 pathway is in play
Summary
The purpose of this review is to give a clinically focused update on the approach to the child with asthma for whom the prescription of a biologic is being considered (omalizumab or mepolizumab, the only ones currently licensed in children), in order to appropriately select those children who need these expensive and invasive medications, to highlight the important differences between adult and paediatric severe asthma with regard to the use of biologicals and to summarise the paediatric biologic data currently published. Personalised asthma medicine was first practiced by the late Dr Harry Morrow-Brown, who used his medical school microscope to show that only those patients with sputum eosinophilia responded to prednisolone and inhaled beclomethasone This meant that two of the most effective asthma therapies that we have were not lost. The eosinophil is important in immunity to parasites, and this may be important in low and middle income (LMIC) settings In this context, it should be noted that the predictive power of blood eosinophil counts for monoclonal responses may be less good than in a high income setting, this has yet to be tested due to poor availability of these medications in LMICs. In summary, the potential beneficial roles of the eosinophil should be considered in the developmental and geographical context of the individual patient when assessing the risks and benefits of anti-IL5 therapy
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