Severe asthma in children: therapeutic considerations

Abstract

Purpose of review Children with poor asthma control despite maximal maintenance therapy have problematic severe asthma (PSA). A step-wise approach including objective adherence monitoring and a detailed multidisciplinary team assessment to identify modifiable factors contributing to poor control is needed prior to considering therapy escalation. Pathophysiological phenotyping in those with true severe therapy-resistant asthma (STRA) and the current array of add-on therapies will be discussed. Recent findings Adherence monitoring using electronic devices has shown that only 20–30% of children with PSA have STRA and need additional therapies. Omalizumab and mepolizumab are licensed for children with STRA aged 6 years and older. Although robust safety and efficacy data, with reduced exacerbations, are available for omalizumab, biomarkers predicting response to treatment are lacking. Paediatric safety data are available for mepolizumab, but efficacy data are unknown for those aged 6–11 years and minimal for those 12 years and older. A sub-group of children with STRA have neutrophilia, but the clinical significance and contribution to disease severity remains uncertain. Summary Most children with PSA have steroid sensitive disease which improves with adherence to maintenance inhaled corticosteroids. Add-on therapies are only needed for the minority with STRA. Paediatric efficacy data of novel biologics and biomarkers that identify the optimal add-on for each child are lacking. If we are to progress toward individualized therapy for STRA, pragmatic clinical trials of biologics in accurately phenotyped children are needed.

EAACI Biologicals Guidelines—Recommendations for severe asthma

“…In children, severe asthma accounts approximately for half of all healthcare resources for paediatric asthma and it is associated with increased risk of mortality, and of development of chronic obstructive pulmonary disease in adulthood. [15][16][17][18][19] The European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines set out a framework for the diagnosis and management of severe asthma in adults and children. 20,21 The Global Initiative for Asthma (GINA) has produced a useful guide for the diagnosis and management of "Difficult-to-treat" and Severe Asthma in adolescents and adults.…”

“…Recommendations follow the evidence-to-decision Tables S44 and S45. As we did not perform a separate analysis for the 12-17 population, recommendations are formulated altogether for the adult and adolescent [12][13][14][15][16][17] population (Box 10).…”

From phenotype to biological treatment of severe asthma

“…long acting β2 agonists, LABA), kako bi se postigla kontrola bolesti, odnosno pokušaj primjene nižeg stupnja liječenja uzrokuje pogoršanja, radi se o teškoj rezistentnoj astmi (1). U ukupnom broju djece s astmom, teška astma prisutna je u 2 do 5% slučajeva, a među njima otprilike jedna trećina ima tešku rezistentnu astmu (2,3). Iako nisko zastupljen kod djece, ovaj fenotip predstavlja zdravstveno i fi nancijsko opterećenje za bolesnika, obitelj i zdravstveni sustav.…”

“…Djelotvornost primjene procjenjuje se nakon 12 do 16 tjedana liječenja, kada treba razmotriti nastavak ili prekid blokade IgE. U oko 30% bolesnika s teškom astmom izostane odgovor na ovaj oblik liječenja (3,25). Smatra se kako je u bolesnika s pozitivnim odgovorom na liječenje korisno produljiti liječenje do najmanje dvije godine (24,26).…”

Immunomodulation in Pediatric Asthma

“…A number of individualized therapies, such as biologics, are available as add-on treatment in adult asthmatic patients with severe uncontrolled symptoms (5). When considering children, only few biologics have been approved and there is limited experience in this population (6) (Table 1).…”